What is an igg food allergy test

Why test IgG for food sensitivity?

Multiple studies propose that the removal of high IgG reactivity foods corresponds to reduced symptoms such as gastrointestinal issues, skin conditions, or migraines, as well as other symptoms people experience as a result of consuming certain foods.

Some studies that are against IgG testing are actually focused on whether IgG testing helps predict or diagnose food allergies, which isn’t how consumers should use our Food Sensitivity test.

What is an igg food allergy test

The Food Sensitivity test isnotan allergy test and we state that clearly on our site.

Here is a list of peer-reviewed studies on IgG food testing and elimination diets

  • Weidlich S, Nennstiel S, Jesinghaus M, Brockow K, et al. IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients. J Clin Gastroenterol. 2020;54(1):43-49. doi: 10.1097/MCG.0000000000001154.
  • Coucke F.

    Food intolerance in patients with manifest autoimmunity. Observational study. Autoimmun Rev. 2018;17(11):1078-1080. doi: 10.1016/j.autrev.2018.05.011. Epub 2018 Sep 11.

  • Tay S, Clark A, Deighton J, King Y, et al. Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin‐specific immunoglobulin responses are ubiquitous, but peanut‐specific immunoglobulin responses are up‐regulated in peanut allergy. Clin Exp Allergy.

    2007;37(10):1512-1518.

  • Severance EG, Dickerson FB, Halling M, et al. Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophr Res. 2010;118(1-3):240-7.doi: 10.1016/j.schres.2009.12.030. Epub 2010 Jan 13.
  • Jian L, Anqi H, Gang L, Litian W, et al. Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study. Inflamm Bowel Dis. 2018;24(9): 1918-1925.
  • Severance EG, Dickerson FB, Halling M, et al. Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophr Res.

    2010;118(1-3):240-7.doi: 10.1016/j.schres.2009.12.030. Epub 2010 Jan 13.

  • Jian L, Anqi H, Gang L, Litian W, et al. Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study. Inflamm Bowel Dis. 2018;24(9): 1918-1925.
  • Kelly DL, Demyanovich HK, Rodriguez KM, et al. Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study. J Psychiatry Neurosci. 2019;44(4):269-276. doi:10.1503/jpn.180174.
  • Zuo XL, Li YQ, Li WJ, Guo YT, et al.

    Alterations of food antigen‐specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy. 2007;37:823-830. doi:10.1111/j.1365-2222.2007.02727.

  • Bernardi D, Borghesan F, Faggian D, Bianchi FC, et al. Time to reconsider the clinical worth of immunoglobulin G4 to foods? Clin Chem Lab Med. 2008;46(5):687-690. doi:10.1515/CCLM.2008.131.
  • Schuyler AJ, Wilson JM, Tripathi A, et al. Specific IgG4 antibodies to cow’s milk proteins in pediatric patients with eosinophilic esophagitis.

    J Allergy Clin Immunol. 2018;142(1):139-148.e12. doi:10.1016/j.jaci.2018.02.049.

  • Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004;53:1459-1464.
  • Karakula-Juchnowicz H, Gałęcka M, Rog J, et al. The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls. Nutrients. 2018;10(5):548.
  • Mitchell N, Hewitt CE, Jayakody S. et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine love headaches.

    Nutr J. 2011;10, 85 doi:10.1186/1475-2891-10-85

  • Schuyler AJ, Wilson JM, Tripathi A, et al. Specific IgG4 antibodies to cow’s milk proteins in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2018;142(1):139-148.e12. doi:10.1016/j.jaci.2018.02.049.
  • Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004;53:1459-1464.
  • Carini C, Fratazzi C, Aiuti F. Immune complexes in food-induced arthralgia. Ann Allergy. 1987;59(6):422-428.
  • Hafström I, Ringertz B, Spångberg A, von Zweigbergk L, et al.

    A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford).2001;40(10):1175-1179.

  • Kelly DL, Demyanovich HK, Rodriguez KM, et al. Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study. J Psychiatry Neurosci. 2019;44(4):269-276. doi:10.1503/jpn.180174.
  • Weidlich S, Nennstiel S, Jesinghaus M, Brockow K, et al. IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients.

    J Clin Gastroenterol. 2020;54(1):43-49. doi: 10.1097/MCG.0000000000001154.

  • Severance, E. G., Dupont, D. , Dickerson, F. B., et al. (2010), Immune activation by casein dietary antigens in bipolar disorder. Bipolar Disorders, 12: 834-842. doi:10.1111/j.1399-5618.2010.00879.
  • Tay S, Clark A, Deighton J, King Y, et al. Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin‐specific immunoglobulin responses are ubiquitous, but peanut‐specific immunoglobulin responses are up‐regulated in peanut allergy.

    Clin Exp Allergy. 2007;37(10):1512-1518.

  • Wright BL, Kulis M, Guo R, et al. Food-specific IgG4 is associated with eosinophilic esophagitis. J Allergy Clin Immunol. 2016;138(4):1190-1192.e3. doi:10.1016/j.jaci.2016.02.024.
  • Alpay, K., Ertas, M., Orhan, E.K., et al. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010;30(7):829–837.

    doi:10.1177/0333102410361404.

  • Bernardi D, Borghesan F, Faggian D, Bianchi FC, et al. Time to reconsider the clinical worth of immunoglobulin G4 to foods? Clin Chem Lab Med. 2008;46(5):687-690. doi:10.1515/CCLM.2008.131.
  • Main J, McKenzie H, Yeaman GR, et al. Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease. BMJ. 1988;297(6656):1105-1106.

    What is an igg food allergy test

    doi:10.1136/bmj.297.6656.1105

  • Zuo XL, Li YQ, Li WJ, Guo YT, et al. Alterations of food antigen‐specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy. 2007;37:823-830. doi:10.1111/j.1365-2222.2007.02727.
  • Aydinlar EI, Dikmen PY, Tiftikci A, et al. IgG‐Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome. Headache. 2013;53:514-525. doi:10.1111/j.1526-4610.2012.02296.
  • Carini C, Fratazzi C, Aiuti F.

    Immune complexes in food-induced arthralgia. Ann Allergy. 1987;59(6):422-428.

  • Mitchell N, Hewitt CE, Jayakody S. et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine love headaches. Nutr J. 2011;10, 85 doi:10.1186/1475-2891-10-85
  • Severance, E. G., Dupont, D. , Dickerson, F. B., et al. (2010), Immune activation by casein dietary antigens in bipolar disorder. Bipolar Disorders, 12: 834-842. doi:10.1111/j.1399-5618.2010.00879.
  • Coucke F. Food intolerance in patients with manifest autoimmunity. Observational study. Autoimmun Rev. 2018;17(11):1078-1080.

    doi: 10.1016/j.autrev.2018.05.011. Epub 2018 Sep 11.

  • Virdee K, Musset J, Baral M, Cronin C, et al. Food-specific IgG Antibody-guided Elimination Diets Followed by Resolution of Asthma Symptoms and Reduction in Pharmacological Interventions in Two Patients: A Case Report. Glob Adv Health Med. 2015;4(1):62-66. doi:10.7453/gahmj.2014.068.a
  • Severance EG, Gressitt KL, Alaedini A, et al. IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia.

    Brain Behav Immun. 2015;44:148-158. doi:10.1016/j.bbi.2014.09.009.

  • Rajendran N, Kumar D. Food‐specific IgG4‐guided exclusion diets improve symptoms in Crohn’s disease: a pilot study. Colorectal Disease. 2011;13:1009-1013. doi:10.1111/j.1463-1318.2010.02373.
  • Zar S, Benson MJ, Kumar D. Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastroenterol. 2005;100(7):1550-1557.
  • Virdee K, Musset J, Baral M, Cronin C, et al. Food-specific IgG Antibody-guided Elimination Diets Followed by Resolution of Asthma Symptoms and Reduction in Pharmacological Interventions in Two Patients: A Case Report.

    Glob Adv Health Med. 2015;4(1):62-66. doi:10.7453/gahmj.2014.068.a

  • Alpay, K., Ertas, M., Orhan, E.K., et al. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010;30(7):829–837. doi:10.1177/0333102410361404.
  • Zar S, Benson MJ, Kumar D. Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastroenterol. 2005;100(7):1550-1557.
  • Aydinlar EI, Dikmen PY, Tiftikci A, et al.

    IgG‐Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome. Headache. 2013;53:514-525. doi:10.1111/j.1526-4610.2012.02296.

  • Karakula-Juchnowicz H, Gałęcka M, Rog J, et al. The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls. Nutrients. 2018;10(5):548.
  • Severance EG, Gressitt KL, Alaedini A, et al. IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia.

    Brain Behav Immun. 2015;44:148-158. doi:10.1016/j.bbi.2014.09.009.

  • Rajendran N, Kumar D. Food‐specific IgG4‐guided exclusion diets improve symptoms in Crohn’s disease: a pilot study. Colorectal Disease. 2011;13:1009-1013. doi:10.1111/j.1463-1318.2010.02373.
  • Lee HS, Lee KJ. Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome. J Neurogastroenterol Motil. 2017;23(4):578-584. doi:10.5056/jnm17054.
  • Lee HS, Lee KJ. Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome.

    J Neurogastroenterol Motil. 2017;23(4):578-584. doi:10.5056/jnm17054.

  • Main J, McKenzie H, Yeaman GR, et al. Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease. BMJ. 1988;297(6656):1105-1106. doi:10.1136/bmj.297.6656.1105
  • Wright BL, Kulis M, Guo R, et al. Food-specific IgG4 is associated with eosinophilic esophagitis. J Allergy Clin Immunol. 2016;138(4):1190-1192.e3. doi:10.1016/j.jaci.2016.02.024.
  • Hafström I, Ringertz B, Spångberg A, von Zweigbergk L, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens.

    Rheumatology (Oxford).2001;40(10):1175-1179.

Food Allergy Testing

There are a variety of ways to test for food allergies. Allergy skin testing is most common in allopathic medicine. In this test, a suspected food allergen is put into solution and then dropped onto the skin. A little prick is made through the drop of the food allergen with a lancet. If the person is allergic to the food, a hive will appear within 20 minutes. This test identifies IgE mediated food allergies.21 This test, however, cannot be used if a person has eczema at the site of testing.

Also, the test may show no reaction to foods that own low levels of IgE.22,23 Likewise, a untrue negative may happen in people taking antihistamines or other immunosuppressive pharmaceuticals. Intradermal skin testing is more sensitive than skin prick testing, but is also more uncomfortable for the patient.24

IgE can also be measured from blood using ELISA (enzyme linked immunosorbant assay).

Advances in technology over the final 10 years own made these tests more common. They are less invasive for the patient than skin tests. The test can report both the presence of an antibody and the relative quantity of the antibody in the serum. However, it is significant to remember that this antibody level will be related to the immediacy of the exposure to the food antigen and to the food antigen that is used by the lab measuring the antibody.

IgG and sIgA ELISA are also becoming favorite, but they own the same drawbacks as IgE ELISA. They are dependent on exposure to a food and on the antigen used in the assay.

Secretory IgA is most often measured from saliva samples, whereas IgG is measured in blood. IgG subclass may influence the correlation between test results and clinical symptoms and is not always reported by the laboratory completing the test. As discussed above, most often IgG1 and IgG4 are elevated in an allergic response. Thus, while ELISA testing is useful in measuring food allergies, it is unable to measure every the reactions that may cause clinical symptoms.

One of the lab tests available for food allergy and sensitivity testing evaluates the change in white blood cell size and number as a measure of reactivity.

It is known that B cells increase in size when they become plasma cells and produce antibodies, T cells increase in size when they produce cytokines, and neutrophils change size when they become activated. However, the lab that uses this method does not report what cells are being measured in their assay, nor do they report the methods of the assay.25

This study compares intralaboratory reliability between 2 types of allergy testing: IgG testing and cell size variability.

The results reported herein propose that IgG testing is more reproducible and dependable than cell size variability. While the initial design included an interlaboratory comparison to see how equivalent the results were of these 2 testing methods, the cell size variability data was not consistent enough to use in a comparison with IgG testing.

References

1.Parker SL, Sussman GL, Krondl M. Dietary aspects of adverse reactions to foods in adults. CMAJ. 1988;October 15; 139(8): 711-718.

2.Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immune.

2006; 117(suppl): S470-5.

3.Zeiger RS. Food allergen avoidance in the prevention of food allergy in infants and children. Pediatrics. 2003; 111(6): 1662-1671.

4.Shamberger R. Types of food allergy testing. The Townsend Letter. 2008; January. 294: 71-72.

5.Breneman J C. Basics of Food Allergy.1978, C. C. Thomas, Springfield, Illinois; p.8.

6.Gaby A. The role of hidden food allergy/intolerance in chronic disease. Alternative Medicine Review. 1998; 3(2): 90-100.

7.Isolauri E, Rautava S, Kalliomaki M. Food allergy in irritable bowel syndrome: new facts and ancient fallacies. Gut. 2004; October. 53(10): 1391-1393.

8.Ortolani C, Bruijnzeel-Koomen C, Bengtsson U, Bindslev-Jensen C, Bjorksten B, Host A, Ispano M et al.

Controversial aspects of adverse reactions to food. Allergy. 1999;54: 27-43.

9.Arshad SH, Tariq SM, Matthews S, Hakim E. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics.2001;Vol. 108, No 2: 33.

10.Kulig M, Bergmann R, Klettke U, Wahn V, Tacke U, Wahn U. Natural course of sensitization to food and inhalant allergens during the first 6 years of life. J Allergy Clin Immunol.1999; June 103(6): 1173-9.

11.Aalberse RC, Van Milligen F, Tan KY, Stapel SO. Allergen-specific IgG4 in atopic disease. Allergy. 1993; 48:559.

12.Burks AW, Laubach S, Jones SM.

Oral tolerance, food allergy, and immunotherapy: Implications for future treatment. J Allergy Clin Immunol. 2008. Article in press.

13.Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, Kleine-Tebbe J, EAACI Task Force. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAAC1 Task Force Report. Allergy. 2008; Jul; 63(7): 793-6.

14.Eysink PE, De Jong MH, Bindels PJ, Scharp-Van Der Linden VT, De Groot CJ, Stapel SO, Aalberse RC. Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study.

Clin Exp Allergy. 1999; May 29 (5): 604-10.

15.Eysink PE, Bindels PJ, Stapel SO, Bottema BJ, Van Der Zee JS, Aalberse RC. Do levels of immunoglobulin G antibodies to foods predict the development of immunoglobulin E antibodies to cat, dog, and/or mite? Clin Exp Allergy. 2002; Apr; 32 (4): 556-62.

16.Wilders-Truschnig M, Mangge H, Lieners C, Gruber M, Mayer C, Marz W. IgG antibodies against food antigens are correlated with inflammation and intima media thickness in obese juveniles.

Exp Clin Endocrinol Diabetes. 2008; Apr 116 (4): 241-S. Epub 2007 Dec 10.

17.Ou-Yang WX, You JY, Duan BP, Chen CB. Application of food allergens specific IgG antibody detection in chronic diarrhea in children. Zhonggua Dang Dai Er Ke ZA Zhi. 2008; Feb 10 (1): 21-4.

18. Wilson CW, Kirker JG, Warnes H, O’Malley M. The clinical features of migraine as a manifestation of allergic disease. Postgrad Med J. 1980; September; 56(659): 617-621.

19.Arroyave Hernandez CM, Echevarria Pinto M, Hernandez Montiel HL. Food allergy mediated by IgG antibodies associated with migraine in adults. Rev Alerg Mex. 2007;Sept-Oct; 54(5): 162-8.

20.Drisko J, Bischoff B, Hall M, McCallum R.

Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics. J Am Coll Nutr. 2006; Dec; 25(6): 514-22.

21.Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomized controlled trial. Gut. 2004; 53:1459-1464.

22.Zar S, Mincher L, Benson MJ, Kumar D. Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome. Scand J Gastroenterol.

2005; Jul; 40(7): 800-7.

23.Atkinson W. 2004. Op cit.

24.Zuo XL, Li YQ, Guo YT, Lu XF, Li JM, Desmond PV. Alterations of food antigen-specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy. 2007; Jun; 37(6): 823-30.

25.Zar S, Benson MJ, Kumar D. Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastroenterol.

2005; Jul. 100(7): 1550-7.

26.Shanahan F, Whorwell PJ. IgG-mediated food intolerance in irritable bowel syndrome: a genuine phenomenon or an epiphenomenom? Am J Gastroenterol. 2005; Jul; 100(7): 1558-9.

27. Drisko J. 2006. Op cit.

28. Ibid.

29.Yang CM, Li YO. The therapeutic effects of eliminating allergic foods according to food-specific IgG antibodies in irritable bowel syndrome. Zhonghua Nei Ke Za Zhi. 2007. Aug; 46(8): 641-3.

30.Staudacer A, Powell BC, Sander GR. Gliadin-induced increase in intestinal epithelial permeability is independent of MEK. Gastroenterology. 2008; 134:A-520.

31.Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Tacono G, Carroccio A, D’Agate C, Not T, Zampini L, Catassi C, Fasano A.

Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006. Apr; 41 (4): 408-19.

32.Hvatum M, Scott H, Brandtzaeg P. Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease. Gut.1992 ;33: 632-638.

33.Wahnschaffe U, Schulzke JD, Zeitz M, Ullrich R. Predictors of clinical response to gluten-free diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol. 2007. Jul; 5(7): 844-50.

34.Sharbati A, Valletta E, Bertini M, Cipolli M, Morroni M, Pinelli L, Tato L. Gluten sensitivity and ‘normal’ histology: is the intestinal mucosa really normal.

Dig Liver Dis. 2003. Nov; 35(1): 768-73.

34.Fine K. Early diagnosis of gluten sensitivity: Before the villi are gone. Greater Louisville Celiac Sprue Support Group. 2003. June.

35.Ibid.

36.Sapone A, Imbrici L, Giuliano MT et al. Role of the immate immune system in the pathogenesis of gluten sensitivity: preliminary study. Gastroenterology. 2008; 134: A-80.


Lauren Russel, ND, received her doctorate in Naturopathic Medicine from Bastyr University in 2006. Previously, she obtained her undergraduate degree in biological sciences from the State University of New York at Stony Brook. Dr. Russel is currently a consulting physician at Meridian Valley Laboratory in Renton, Washington, a medical author and editor, and in private practice in Lynnwood, Washington.

Leah Alvarado-Paz, ND, received her Naturopathic degree from Bastyr University in 2006.

Her undergraduate degree in Molecular and Cellular Biology was received from Texas A&M University. Dr. Alvarado-Paz is currently a consulting physician at Meridian Valley Laboratory.

IgG blood testing for delayed food allergies?

  1. Alpay, K., Ertas, M., Orhan, E.K., et al. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010;30(7):829–837. doi:10.1177/0333102410361404.
  2. Severance, E. G., Dupont, D. , Dickerson, F. B., et al. (2010), Immune activation by casein dietary antigens in bipolar disorder.

    Bipolar Disorders, 12: 834-842. doi:10.1111/j.1399-5618.2010.00879.

  3. Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004;53:1459-1464.
  4. Schuyler AJ, Wilson JM, Tripathi A, et al. Specific IgG4 antibodies to cow’s milk proteins in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2018;142(1):139-148.e12. doi:10.1016/j.jaci.2018.02.049.
  5. Carini C, Fratazzi C, Aiuti F. Immune complexes in food-induced arthralgia. Ann Allergy. 1987;59(6):422-428.
  6. Mitchell N, Hewitt CE, Jayakody S.

    et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine love headaches. Nutr J. 2011;10, 85 doi:10.1186/1475-2891-10-85

  7. Main J, McKenzie H, Yeaman GR, et al. Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease. BMJ. 1988;297(6656):1105-1106. doi:10.1136/bmj.297.6656.1105
  8. Wright BL, Kulis M, Guo R, et al. Food-specific IgG4 is associated with eosinophilic esophagitis. J Allergy Clin Immunol. 2016;138(4):1190-1192.e3. doi:10.1016/j.jaci.2016.02.024.
  9. Tay S, Clark A, Deighton J, King Y, et al. Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin‐specific immunoglobulin responses are ubiquitous, but peanut‐specific immunoglobulin responses are up‐regulated in peanut allergy.

    Clin Exp Allergy. 2007;37(10):1512-1518.

  10. Coucke F. Food intolerance in patients with manifest autoimmunity. Observational study. Autoimmun Rev. 2018;17(11):1078-1080. doi: 10.1016/j.autrev.2018.05.011. Epub 2018 Sep 11.
  11. Karakula-Juchnowicz H, Gałęcka M, Rog J, et al. The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls. Nutrients. 2018;10(5):548.
  12. Weidlich S, Nennstiel S, Jesinghaus M, Brockow K, et al. IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients.

    J Clin Gastroenterol. 2020;54(1):43-49. doi: 10.1097/MCG.0000000000001154.

  13. Jian L, Anqi H, Gang L, Litian W, et al. Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study. Inflamm Bowel Dis. 2018;24(9): 1918-1925.
  14. Aydinlar EI, Dikmen PY, Tiftikci A, et al. IgG‐Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome. Headache. 2013;53:514-525. doi:10.1111/j.1526-4610.2012.02296.
  15. Rajendran N, Kumar D. Food‐specific IgG4‐guided exclusion diets improve symptoms in Crohn’s disease: a pilot study.

    Colorectal Disease. 2011;13:1009-1013. doi:10.1111/j.1463-1318.2010.02373.

  16. Severance EG, Gressitt KL, Alaedini A, et al. IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia. Brain Behav Immun. 2015;44:148-158. doi:10.1016/j.bbi.2014.09.009.
  17. Lee HS, Lee KJ. Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome. J Neurogastroenterol Motil. 2017;23(4):578-584. doi:10.5056/jnm17054.
  18. Virdee K, Musset J, Baral M, Cronin C, et al. Food-specific IgG Antibody-guided Elimination Diets Followed by Resolution of Asthma Symptoms and Reduction in Pharmacological Interventions in Two Patients: A Case Report.

    Glob Adv Health Med. 2015;4(1):62-66. doi:10.7453/gahmj.2014.068.a

  19. Zar S, Benson MJ, Kumar D. Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastroenterol. 2005;100(7):1550-1557.
  20. Kelly DL, Demyanovich HK, Rodriguez KM, et al. Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study. J Psychiatry Neurosci. 2019;44(4):269-276. doi:10.1503/jpn.180174.
  21. Bernardi D, Borghesan F, Faggian D, Bianchi FC, et al. Time to reconsider the clinical worth of immunoglobulin G4 to foods?

    Clin Chem Lab Med. 2008;46(5):687-690. doi:10.1515/CCLM.2008.131.

  22. Zuo XL, Li YQ, Li WJ, Guo YT, et al. Alterations of food antigen‐specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy. 2007;37:823-830. doi:10.1111/j.1365-2222.2007.02727.
  23. Severance EG, Dickerson FB, Halling M, et al. Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophr Res. 2010;118(1-3):240-7.doi: 10.1016/j.schres.2009.12.030.

    Epub 2010 Jan 13.

  24. Hafström I, Ringertz B, Spångberg A, von Zweigbergk L, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford).2001;40(10):1175-1179.

Q. A family member had a blood test called IgG to check for any delayed allergies. It showed milk and eggs to be a severe, but delayed allergy (no skin reaction). Is there a blood test that can check if she has a delayed allergy to other birds’ eggs (i.e.

turkey, duck, quail, etc.) and other animals’ milk (i.e. goat milk, sheep milk, or maybe unpasteurized raw cow milk, etc.)?

A. In IgG testing, the blood is tested for IgG antibodies instead of being tested for IgE antibodies (the antibodies associated with food allergies). IgG is a “memory antibody”.
When you own a blood test to query response to an immunization, this is also IgG testing. A common example is a “Rubella titer”.
In the context of food, IgG signifies memory through exposure to a food. Because a normal immune system should make IgG antibodies to foreign proteins (to include foods), a positive IgG test to a food is a sign of a normal immune system, and suggests tolerance or “memory” of the food rather than food allergy.

Therefore, IgG testing is not recommended for evaluation of food allergies.
If the patient has previously eaten the food (milks, eggs), he or she would likely own IgG to the food.

Q. My son was diagnosed with peanut allergy by screening blood testing when he was 18 months ancient (done for a family history of food allergy in first cousins) but he never had a major reaction to peanut before the diagnosis, and nothing has happened since. He is now 5 years ancient.

He has had cookies that were made in a facility where peanuts are present, without any reaction. He recently had a negative skin test for peanut and his final blood test level was 2.3. I was told that my son should continue to avoid peanuts. However, I recently read about a new helpful of blood test for peanut allergy, and I am wondering if this test could be helpful for my son?

A. Peanut allergy seems to be on the rise in the US over the past decade. While there are some promising treatments being researched, the current standard of care is finish avoidance of peanut. Because this restriction can own such a major impact on everyone involved, it is extremely significant that you get an precise diagnosis.

Peanut allergy affects most areas of a person s life, from the home setting, to frolic dates, to school, to dining out and beyond.The most significant factor in making an precise diagnosis of peanut allergy is the actual history of the type of reaction that occurred upon consuming a peanut. Specific IgE blood tests (like ImmunoCAP, a common test) and skin prick tests are used in combination with the clinical history to make a diagnosis. In some cases an allergist-supervised oral food challenge is recommended, and this is, in fact, considered the gold standard for precise diagnosis of allergy to peanut. (This same approach is applied to any possible IgE-mediated food allergy, not just to peanut.)One problem that allergists face is that some people do not own a clear-cut history of reaction to peanut.

Situations that allergists see frequently include:In these cases, allergists will typically act out a skin prick test to acquire more information. If the skin test is negative, a specific IgE blood test such as ImmunoCAP test can be ordered to acquire more information. If the test comes back negative (meaning finish absence of peanut-specific IgE or a extremely low positive result with no history of anaphylaxis or other serious reaction), an allergist will often proceed to an oral food challenge in the office to confirm the test results,However, if the first blood test comes back positive, yet the clinical history is vague or indicates a mild reaction history, a new test, called the peanut «component test», can be ordered to acquire more information in this situation.

This component test — the one you are asking about — can determine which specific peanut proteins are triggering the positive test results. It is significant to note that there are numerous smaller protein fragments that make up a whole peanut. Thus, when a person reacts to peanut, he or she may be responding to one or more diverse protein fragments in the peanut. Determining which of these protein pieces are causing the reaction is significant, as some (scientific names Ara h 1 , Ara h 2 , and Ara h 3 ) carry more risk than others.

Thus, if these specific tests are negative, there is less risk, and if positive, there is more risk. This will assist guide whether an oral food challenge would still be okay (despite the positive initial peanut blood test).Given your son s unclear history of reaction to peanut, we would recommend that you speak to your allergist about the peanut component test and a possible oral food challenge depending on the results of the test. The information gained from the test will be helpful to you, either way!

See the original questions and answers here at the American College of Allergy, Asthma & Immunology

Abstract

The ability to identify and eliminate food allergens in the diet affects an individual’s health.

Thus, clinicians need a dependable and reproducible way to identify foods allergies or sensitivities for their patients. Objective: To compare and test the reliability and consistency of 2 diverse food allergy testing methods: cell size allergy testing versus IgG ELISA food allergy testing within the same donor. Design: Blood samples from a single donor were sent to 2 diverse food allergy testing labs under diverse names. Both laboratories used diverse food allergy testing methods.

Two samples were sent to each lab on the first day (split sample), and 2 more samples were sent to each lab over the course of the following week (4 samples sent to each lab in the same week). The results from these tests were evaluated 3 ways: 1) within test repeatability on a divide sample; 2) within test variability over the course of a week; and 3) interlaboratory variability between the 2 testing methods. Outcomes: Reaction results from both testing methods were reported as no reaction, low reaction, moderate reaction, or high reaction. Reactions to individual foods were evaluated and compared statistically between diverse time points. Results: The IgG ELISA food allergy testing method showed consistency both in a divide sample on a single day and over the course of a week in the reported results.

The cell size testing method generated random results for divide samples in both time periods in both time periods (split sample and over a week). Conclusion: This study calls into question the reliability of blood cell size testing as a method for identifying food allergies. While the sample size was little, these tests are completed for individual patients in a clinical setting and thus, variability must be minimal for the test to be clinically valid. IgG food allergy testing was reproducible and dependable in this study.

Why test IgG for food sensitivity?

Multiple studies propose that the removal of high IgG reactivity foods corresponds to reduced symptoms such as gastrointestinal issues, skin conditions, or migraines, as well as other symptoms people experience as a result of consuming certain foods.

Some studies that are against IgG testing are actually focused on whether IgG testing helps predict or diagnose food allergies, which isn’t how consumers should use our Food Sensitivity test. The Food Sensitivity test isnotan allergy test and we state that clearly on our site.

Here is a list of peer-reviewed studies on IgG food testing and elimination diets

Food Allergy Testing

There are a variety of ways to test for food allergies. Allergy skin testing is most common in allopathic medicine. In this test, a suspected food allergen is put into solution and then dropped onto the skin.

A little prick is made through the drop of the food allergen with a lancet. If the person is allergic to the food, a hive will appear within 20 minutes. This test identifies IgE mediated food allergies.21 This test, however, cannot be used if a person has eczema at the site of testing. Also, the test may show no reaction to foods that own low levels of IgE.22,23 Likewise, a untrue negative may happen in people taking antihistamines or other immunosuppressive pharmaceuticals. Intradermal skin testing is more sensitive than skin prick testing, but is also more uncomfortable for the patient.24

IgE can also be measured from blood using ELISA (enzyme linked immunosorbant assay).

Advances in technology over the final 10 years own made these tests more common. They are less invasive for the patient than skin tests. The test can report both the presence of an antibody and the relative quantity of the antibody in the serum. However, it is significant to remember that this antibody level will be related to the immediacy of the exposure to the food antigen and to the food antigen that is used by the lab measuring the antibody.

IgG and sIgA ELISA are also becoming favorite, but they own the same drawbacks as IgE ELISA. They are dependent on exposure to a food and on the antigen used in the assay. Secretory IgA is most often measured from saliva samples, whereas IgG is measured in blood.

IgG subclass may influence the correlation between test results and clinical symptoms and is not always reported by the laboratory completing the test. As discussed above, most often IgG1 and IgG4 are elevated in an allergic response. Thus, while ELISA testing is useful in measuring food allergies, it is unable to measure every the reactions that may cause clinical symptoms.

One of the lab tests available for food allergy and sensitivity testing evaluates the change in white blood cell size and number as a measure of reactivity. It is known that B cells increase in size when they become plasma cells and produce antibodies, T cells increase in size when they produce cytokines, and neutrophils change size when they become activated.

However, the lab that uses this method does not report what cells are being measured in their assay, nor do they report the methods of the assay.25

This study compares intralaboratory reliability between 2 types of allergy testing: IgG testing and cell size variability. The results reported herein propose that IgG testing is more reproducible and dependable than cell size variability.

While the initial design included an interlaboratory comparison to see how equivalent the results were of these 2 testing methods, the cell size variability data was not consistent enough to use in a comparison with IgG testing.

References

1.Parker SL, Sussman GL, Krondl M. Dietary aspects of adverse reactions to foods in adults. CMAJ. 1988;October 15; 139(8): 711-718.

2.Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immune. 2006; 117(suppl): S470-5.

3.Zeiger RS. Food allergen avoidance in the prevention of food allergy in infants and children.

Pediatrics. 2003; 111(6): 1662-1671.

4.Shamberger R. Types of food allergy testing. The Townsend Letter. 2008; January. 294: 71-72.

5.Breneman J C. Basics of Food Allergy.1978, C. C. Thomas, Springfield, Illinois; p.8.

6.Gaby A. The role of hidden food allergy/intolerance in chronic disease. Alternative Medicine Review. 1998; 3(2): 90-100.

7.Isolauri E, Rautava S, Kalliomaki M. Food allergy in irritable bowel syndrome: new facts and ancient fallacies. Gut. 2004; October. 53(10): 1391-1393.

8.Ortolani C, Bruijnzeel-Koomen C, Bengtsson U, Bindslev-Jensen C, Bjorksten B, Host A, Ispano M et al.

Controversial aspects of adverse reactions to food. Allergy. 1999;54: 27-43.

9.Arshad SH, Tariq SM, Matthews S, Hakim E. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics.2001;Vol. 108, No 2: 33.

10.Kulig M, Bergmann R, Klettke U, Wahn V, Tacke U, Wahn U. Natural course of sensitization to food and inhalant allergens during the first 6 years of life. J Allergy Clin Immunol.1999; June 103(6): 1173-9.

11.Aalberse RC, Van Milligen F, Tan KY, Stapel SO.

Allergen-specific IgG4 in atopic disease. Allergy. 1993; 48:559.

12.Burks AW, Laubach S, Jones SM. Oral tolerance, food allergy, and immunotherapy: Implications for future treatment. J Allergy Clin Immunol. 2008. Article in press.

13.Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, Kleine-Tebbe J, EAACI Task Force. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAAC1 Task Force Report. Allergy. 2008; Jul; 63(7): 793-6.

14.Eysink PE, De Jong MH, Bindels PJ, Scharp-Van Der Linden VT, De Groot CJ, Stapel SO, Aalberse RC. Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study.

Clin Exp Allergy. 1999; May 29 (5): 604-10.

15.Eysink PE, Bindels PJ, Stapel SO, Bottema BJ, Van Der Zee JS, Aalberse RC. Do levels of immunoglobulin G antibodies to foods predict the development of immunoglobulin E antibodies to cat, dog, and/or mite? Clin Exp Allergy. 2002; Apr; 32 (4): 556-62.

16.Wilders-Truschnig M, Mangge H, Lieners C, Gruber M, Mayer C, Marz W. IgG antibodies against food antigens are correlated with inflammation and intima media thickness in obese juveniles. Exp Clin Endocrinol Diabetes. 2008; Apr 116 (4): 241-S.

Epub 2007 Dec 10.

17.Ou-Yang WX, You JY, Duan BP, Chen CB. Application of food allergens specific IgG antibody detection in chronic diarrhea in children. Zhonggua Dang Dai Er Ke ZA Zhi. 2008; Feb 10 (1): 21-4.

18. Wilson CW, Kirker JG, Warnes H, O’Malley M. The clinical features of migraine as a manifestation of allergic disease. Postgrad Med J. 1980; September; 56(659): 617-621.

19.Arroyave Hernandez CM, Echevarria Pinto M, Hernandez Montiel HL. Food allergy mediated by IgG antibodies associated with migraine in adults. Rev Alerg Mex. 2007;Sept-Oct; 54(5): 162-8.

20.Drisko J, Bischoff B, Hall M, McCallum R.

Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics. J Am Coll Nutr. 2006; Dec; 25(6): 514-22.

21.Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomized controlled trial. Gut. 2004; 53:1459-1464.

22.Zar S, Mincher L, Benson MJ, Kumar D. Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome.

Scand J Gastroenterol. 2005; Jul; 40(7): 800-7.

23.Atkinson W. 2004. Op cit.

24.Zuo XL, Li YQ, Guo YT, Lu XF, Li JM, Desmond PV. Alterations of food antigen-specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy. 2007; Jun; 37(6): 823-30.

25.Zar S, Benson MJ, Kumar D. Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastroenterol. 2005; Jul. 100(7): 1550-7.

26.Shanahan F, Whorwell PJ. IgG-mediated food intolerance in irritable bowel syndrome: a genuine phenomenon or an epiphenomenom?

Am J Gastroenterol. 2005; Jul; 100(7): 1558-9.

27. Drisko J. 2006. Op cit.

28. Ibid.

29.Yang CM, Li YO. The therapeutic effects of eliminating allergic foods according to food-specific IgG antibodies in irritable bowel syndrome. Zhonghua Nei Ke Za Zhi. 2007. Aug; 46(8): 641-3.

30.Staudacer A, Powell BC, Sander GR. Gliadin-induced increase in intestinal epithelial permeability is independent of MEK. Gastroenterology. 2008; 134:A-520.

31.Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Tacono G, Carroccio A, D’Agate C, Not T, Zampini L, Catassi C, Fasano A. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.

Scand J Gastroenterol. 2006. Apr; 41 (4): 408-19.

32.Hvatum M, Scott H, Brandtzaeg P. Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease. Gut.1992 ;33: 632-638.

33.Wahnschaffe U, Schulzke JD, Zeitz M, Ullrich R. Predictors of clinical response to gluten-free diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol. 2007. Jul; 5(7): 844-50.

34.Sharbati A, Valletta E, Bertini M, Cipolli M, Morroni M, Pinelli L, Tato L. Gluten sensitivity and ‘normal’ histology: is the intestinal mucosa really normal.

Dig Liver Dis. 2003. Nov; 35(1): 768-73.

34.Fine K. Early diagnosis of gluten sensitivity: Before the villi are gone. Greater Louisville Celiac Sprue Support Group. 2003. June.

35.Ibid.

36.Sapone A, Imbrici L, Giuliano MT et al. Role of the immate immune system in the pathogenesis of gluten sensitivity: preliminary study. Gastroenterology. 2008; 134: A-80.


Lauren Russel, ND, received her doctorate in Naturopathic Medicine from Bastyr University in 2006.

Previously, she obtained her undergraduate degree in biological sciences from the State University of New York at Stony Brook. Dr. Russel is currently a consulting physician at Meridian Valley Laboratory in Renton, Washington, a medical author and editor, and in private practice in Lynnwood, Washington.

Leah Alvarado-Paz, ND, received her Naturopathic degree from Bastyr University in 2006. Her undergraduate degree in Molecular and Cellular Biology was received from Texas A&M University. Dr. Alvarado-Paz is currently a consulting physician at Meridian Valley Laboratory.

IgG blood testing for delayed food allergies?

  1. Alpay, K., Ertas, M., Orhan, E.K., et al. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010;30(7):829–837. doi:10.1177/0333102410361404.
  2. Severance, E. G., Dupont, D. , Dickerson, F. B., et al. (2010), Immune activation by casein dietary antigens in bipolar disorder. Bipolar Disorders, 12: 834-842. doi:10.1111/j.1399-5618.2010.00879.
  3. Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial.

    Gut. 2004;53:1459-1464.

  4. Schuyler AJ, Wilson JM, Tripathi A, et al. Specific IgG4 antibodies to cow’s milk proteins in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2018;142(1):139-148.e12. doi:10.1016/j.jaci.2018.02.049.
  5. Carini C, Fratazzi C, Aiuti F. Immune complexes in food-induced arthralgia. Ann Allergy. 1987;59(6):422-428.
  6. Mitchell N, Hewitt CE, Jayakody S. et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine love headaches.

    Nutr J. 2011;10, 85 doi:10.1186/1475-2891-10-85

  7. Main J, McKenzie H, Yeaman GR, et al. Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease. BMJ. 1988;297(6656):1105-1106. doi:10.1136/bmj.297.6656.1105
  8. Wright BL, Kulis M, Guo R, et al. Food-specific IgG4 is associated with eosinophilic esophagitis. J Allergy Clin Immunol. 2016;138(4):1190-1192.e3.

    doi:10.1016/j.jaci.2016.02.024.

  9. Tay S, Clark A, Deighton J, King Y, et al. Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin‐specific immunoglobulin responses are ubiquitous, but peanut‐specific immunoglobulin responses are up‐regulated in peanut allergy. Clin Exp Allergy. 2007;37(10):1512-1518.
  10. Coucke F. Food intolerance in patients with manifest autoimmunity. Observational study. Autoimmun Rev. 2018;17(11):1078-1080. doi: 10.1016/j.autrev.2018.05.011. Epub 2018 Sep 11.
  11. Karakula-Juchnowicz H, Gałęcka M, Rog J, et al. The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls.

    Nutrients. 2018;10(5):548.

  12. Weidlich S, Nennstiel S, Jesinghaus M, Brockow K, et al. IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients. J Clin Gastroenterol. 2020;54(1):43-49. doi: 10.1097/MCG.0000000000001154.
  13. Jian L, Anqi H, Gang L, Litian W, et al. Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study. Inflamm Bowel Dis.

    2018;24(9): 1918-1925.

  14. Aydinlar EI, Dikmen PY, Tiftikci A, et al. IgG‐Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome. Headache. 2013;53:514-525. doi:10.1111/j.1526-4610.2012.02296.
  15. Rajendran N, Kumar D. Food‐specific IgG4‐guided exclusion diets improve symptoms in Crohn’s disease: a pilot study. Colorectal Disease. 2011;13:1009-1013. doi:10.1111/j.1463-1318.2010.02373.
  16. Severance EG, Gressitt KL, Alaedini A, et al. IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia. Brain Behav Immun. 2015;44:148-158. doi:10.1016/j.bbi.2014.09.009.
  17. Lee HS, Lee KJ.

    Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome. J Neurogastroenterol Motil. 2017;23(4):578-584. doi:10.5056/jnm17054.

  18. Virdee K, Musset J, Baral M, Cronin C, et al. Food-specific IgG Antibody-guided Elimination Diets Followed by Resolution of Asthma Symptoms and Reduction in Pharmacological Interventions in Two Patients: A Case Report. Glob Adv Health Med. 2015;4(1):62-66. doi:10.7453/gahmj.2014.068.a
  19. Zar S, Benson MJ, Kumar D. Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastroenterol.

    2005;100(7):1550-1557.

  20. Kelly DL, Demyanovich HK, Rodriguez KM, et al. Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study. J Psychiatry Neurosci. 2019;44(4):269-276. doi:10.1503/jpn.180174.
  21. Bernardi D, Borghesan F, Faggian D, Bianchi FC, et al. Time to reconsider the clinical worth of immunoglobulin G4 to foods? Clin Chem Lab Med. 2008;46(5):687-690. doi:10.1515/CCLM.2008.131.
  22. Zuo XL, Li YQ, Li WJ, Guo YT, et al.

    Alterations of food antigen‐specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy. 2007;37:823-830. doi:10.1111/j.1365-2222.2007.02727.

  23. Severance EG, Dickerson FB, Halling M, et al. Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophr Res. 2010;118(1-3):240-7.doi: 10.1016/j.schres.2009.12.030. Epub 2010 Jan 13.
  24. Hafström I, Ringertz B, Spångberg A, von Zweigbergk L, et al.

    A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford).2001;40(10):1175-1179.

Q. A family member had a blood test called IgG to check for any delayed allergies. It showed milk and eggs to be a severe, but delayed allergy (no skin reaction). Is there a blood test that can check if she has a delayed allergy to other birds’ eggs (i.e.

turkey, duck, quail, etc.) and other animals’ milk (i.e. goat milk, sheep milk, or maybe unpasteurized raw cow milk, etc.)?

A. In IgG testing, the blood is tested for IgG antibodies instead of being tested for IgE antibodies (the antibodies associated with food allergies). IgG is a “memory antibody”.
When you own a blood test to query response to an immunization, this is also IgG testing. A common example is a “Rubella titer”.

In the context of food, IgG signifies memory through exposure to a food. Because a normal immune system should make IgG antibodies to foreign proteins (to include foods), a positive IgG test to a food is a sign of a normal immune system, and suggests tolerance or “memory” of the food rather than food allergy. Therefore, IgG testing is not recommended for evaluation of food allergies.
If the patient has previously eaten the food (milks, eggs), he or she would likely own IgG to the food.

Q. My son was diagnosed with peanut allergy by screening blood testing when he was 18 months ancient (done for a family history of food allergy in first cousins) but he never had a major reaction to peanut before the diagnosis, and nothing has happened since. He is now 5 years ancient. He has had cookies that were made in a facility where peanuts are present, without any reaction. He recently had a negative skin test for peanut and his final blood test level was 2.3. I was told that my son should continue to avoid peanuts. However, I recently read about a new helpful of blood test for peanut allergy, and I am wondering if this test could be helpful for my son?

A. Peanut allergy seems to be on the rise in the US over the past decade. While there are some promising treatments being researched, the current standard of care is finish avoidance of peanut. Because this restriction can own such a major impact on everyone involved, it is extremely significant that you get an precise diagnosis. Peanut allergy affects most areas of a person s life, from the home setting, to frolic dates, to school, to dining out and beyond.The most significant factor in making an precise diagnosis of peanut allergy is the actual history of the type of reaction that occurred upon consuming a peanut.

Specific IgE blood tests (like ImmunoCAP, a common test) and skin prick tests are used in combination with the clinical history to make a diagnosis. In some cases an allergist-supervised oral food challenge is recommended, and this is, in fact, considered the gold standard for precise diagnosis of allergy to peanut. (This same approach is applied to any possible IgE-mediated food allergy, not just to peanut.)One problem that allergists face is that some people do not own a clear-cut history of reaction to peanut.

Situations that allergists see frequently include:In these cases, allergists will typically act out a skin prick test to acquire more information. If the skin test is negative, a specific IgE blood test such as ImmunoCAP test can be ordered to acquire more information. If the test comes back negative (meaning finish absence of peanut-specific IgE or a extremely low positive result with no history of anaphylaxis or other serious reaction), an allergist will often proceed to an oral food challenge in the office to confirm the test results,However, if the first blood test comes back positive, yet the clinical history is vague or indicates a mild reaction history, a new test, called the peanut «component test», can be ordered to acquire more information in this situation.

This component test — the one you are asking about — can determine which specific peanut proteins are triggering the positive test results. It is significant to note that there are numerous smaller protein fragments that make up a whole peanut. Thus, when a person reacts to peanut, he or she may be responding to one or more diverse protein fragments in the peanut. Determining which of these protein pieces are causing the reaction is significant, as some (scientific names Ara h 1 , Ara h 2 , and Ara h 3 ) carry more risk than others.

Thus, if these specific tests are negative, there is less risk, and if positive, there is more risk. This will assist guide whether an oral food challenge would still be okay (despite the positive initial peanut blood test).Given your son s unclear history of reaction to peanut, we would recommend that you speak to your allergist about the peanut component test and a possible oral food challenge depending on the results of the test. The information gained from the test will be helpful to you, either way!

See the original questions and answers here at the American College of Allergy, Asthma & Immunology

Abstract

The ability to identify and eliminate food allergens in the diet affects an individual’s health. Thus, clinicians need a dependable and reproducible way to identify foods allergies or sensitivities for their patients. Objective: To compare and test the reliability and consistency of 2 diverse food allergy testing methods: cell size allergy testing versus IgG ELISA food allergy testing within the same donor.

Design: Blood samples from a single donor were sent to 2 diverse food allergy testing labs under diverse names. Both laboratories used diverse food allergy testing methods. Two samples were sent to each lab on the first day (split sample), and 2 more samples were sent to each lab over the course of the following week (4 samples sent to each lab in the same week).

What is an igg food allergy test

The results from these tests were evaluated 3 ways: 1) within test repeatability on a divide sample; 2) within test variability over the course of a week; and 3) interlaboratory variability between the 2 testing methods. Outcomes: Reaction results from both testing methods were reported as no reaction, low reaction, moderate reaction, or high reaction. Reactions to individual foods were evaluated and compared statistically between diverse time points.

Results: The IgG ELISA food allergy testing method showed consistency both in a divide sample on a single day and over the course of a week in the reported results. The cell size testing method generated random results for divide samples in both time periods in both time periods (split sample and over a week). Conclusion: This study calls into question the reliability of blood cell size testing as a method for identifying food allergies. While the sample size was little, these tests are completed for individual patients in a clinical setting and thus, variability must be minimal for the test to be clinically valid.

IgG food allergy testing was reproducible and dependable in this study.

Why test IgG for food sensitivity?

Multiple studies propose that the removal of high IgG reactivity foods corresponds to reduced symptoms such as gastrointestinal issues, skin conditions, or migraines, as well as other symptoms people experience as a result of consuming certain foods.

Some studies that are against IgG testing are actually focused on whether IgG testing helps predict or diagnose food allergies, which isn’t how consumers should use our Food Sensitivity test.

The Food Sensitivity test isnotan allergy test and we state that clearly on our site.

Here is a list of peer-reviewed studies on IgG food testing and elimination diets

  • 12. Severance EG, et al Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophr Res. 2010;118:240-7.

  • 5. Drisko J, Bischoff B, Hall M, McCallum R, Treating Irritable Bowel Syndrome with a Food Elimination Diet Followed by Food Challenge and Probiotics. Journal of the American College of Nutrition 2006; 25: 514–522

  • Tay S, Clark A, Deighton J, King Y, et al. Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin‐specific immunoglobulin responses are ubiquitous, but peanut‐specific immunoglobulin responses are up‐regulated in peanut allergy.

    Clin Exp Allergy. 2007;37(10):1512-1518.

  • Alpay, K., Ertas, M., Orhan, E.K., et al. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010;30(7):829–837. doi:10.1177/0333102410361404.
  • Karakula-Juchnowicz H, Gałęcka M, Rog J, et al. The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls. Nutrients. 2018;10(5):548.
  • 9. M Hadjivassiliou, R A Grünewald, G A B Davies-Jones Gluten sensitivity as a neurological illness.

    Neurol Neurosurg Psychiatry 2002;72:560–563

  • 16. Marijn van der Neut Kolfschoten, et al Anti-Inflammatory Activity of Human IgG4 Antibodies by Dynamic Fab Arm Exchange. Science 2007;317:1554-1555

  • Severance, E. G., Dupont, D. , Dickerson, F. B., et al. (2010), Immune activation by casein dietary antigens in bipolar disorder. Bipolar Disorders, 12: 834-842. doi:10.1111/j.1399-5618.2010.00879.
  • Atkinson W, Sheldon TA, Shaath N, et al.

    Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004;53:1459-1464.

  • Schuyler AJ, Wilson JM, Tripathi A, et al. Specific IgG4 antibodies to cow’s milk proteins in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2018;142(1):139-148.e12. doi:10.1016/j.jaci.2018.02.049.
  • Weidlich S, Nennstiel S, Jesinghaus M, Brockow K, et al. IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients.

    J Clin Gastroenterol.

    What is an igg food allergy test

    2020;54(1):43-49. doi: 10.1097/MCG.0000000000001154.

  • Carini C, Fratazzi C, Aiuti F. Immune complexes in food-induced arthralgia. Ann Allergy. 1987;59(6):422-428.
  • Lee HS, Lee KJ. Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome. J Neurogastroenterol Motil. 2017;23(4):578-584. doi:10.5056/jnm17054.
  • 13.Huber A, et al Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Int Arch Allergy Immunol. 1998; 115:67-72.

  • Hafström I, Ringertz B, Spångberg A, von Zweigbergk L, et al.

    A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford).2001;40(10):1175-1179.

  • Bernardi D, Borghesan F, Faggian D, Bianchi FC, et al. Time to reconsider the clinical worth of immunoglobulin G4 to foods? Clin Chem Lab Med. 2008;46(5):687-690. doi:10.1515/CCLM.2008.131.
  • 11. Severance EG et al Immune activation by casein dietary antigens in bipolar disorder. Bipolar Disord 2010;12: 834–842

  • Kelly DL, Demyanovich HK, Rodriguez KM, et al.

    Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study. J Psychiatry Neurosci. 2019;44(4):269-276. doi:10.1503/jpn.180174.

  • 14.Vance G. et al. Ovalbumin specific immunoglobulin G and subclass responses through the first five years of life in relation to duration of sensitization and the development of asthma. Clia Exp Allergy 2004;34:1452-1459

  • Wright BL, Kulis M, Guo R, et al. Food-specific IgG4 is associated with eosinophilic esophagitis. J Allergy Clin Immunol. 2016;138(4):1190-1192.e3.

    doi:10.1016/j.jaci.2016.02.024.

  • Zuo XL, Li YQ, Li WJ, Guo YT, et al. Alterations of food antigen‐specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy. 2007;37:823-830. doi:10.1111/j.1365-2222.2007.02727.
  • 7.Janice Main, Hamish McKenzie, Grant R Yeaman, Michael A Kerr, Deborah Robson, Christopher R Pennington, David Parratt Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease BMJ 1988;297:1105-1106

  • Rajendran N, Kumar D.

    Food‐specific IgG4‐guided exclusion diets improve symptoms in Crohn’s disease: a pilot study. Colorectal Disease. 2011;13:1009-1013. doi:10.1111/j.1463-1318.2010.02373.

  • Severance EG, Dickerson FB, Halling M, et al. Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophr Res. 2010;118(1-3):240-7.doi: 10.1016/j.schres.2009.12.030.

    Epub 2010 Jan 13.

  • 15.Wilders-Truschnig M et al. IgG Antibodies Against Food Antigens are Correlated with Inflammation and Intima Media Thickness in Obese Juveniles. Exp Clin Endocrinol Diabetes 2008;116:241-5.

  • 1. Statement of the AAAAI Work Group Report: Current Approach to the Diagnosis and Management of Adverse Reactions to Foods, October 2003. http://www.aaaai.org/ask-the-expert/usefulness-of-measurements-of-IgG-antibody.aspx (Accessed October 27,2013).

  • 8. Thomas Schaffer, Stefan Mueller, , Beatrice Flogerzi, , Beatrice Seibold-Schmid,Alain M.

    Schoepfer, and Candid Seibold Anti-Saccharomyces cerevisiae Mannan Antibodies (ASCA) of Crohn’s Patients Crossreact with Mannan from Other Yeast Strains, and Murine ASCA IgM Can Be Experimentally Induced with Candida albicans Inflamm Bowel Dis 2007;13:1339 –1346

  • 3. Nagisa Sugaya N and Nomura S, Relationship between cognitive appraisals of symptoms and negative mood for subtypes of irritable bowel syndrome. BioPsychoSocial Medicine 2008;2:9-14

  • Severance EG, Gressitt KL, Alaedini A, et al.

    IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia. Brain Behav Immun. 2015;44:148-158. doi:10.1016/j.bbi.2014.09.009.

  • Jian L, Anqi H, Gang L, Litian W, et al. Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study. Inflamm Bowel Dis. 2018;24(9): 1918-1925.
  • Virdee K, Musset J, Baral M, Cronin C, et al.

    Food-specific IgG Antibody-guided Elimination Diets Followed by Resolution of Asthma Symptoms and Reduction in Pharmacological Interventions in Two Patients: A Case Report. Glob Adv Health Med. 2015;4(1):62-66. doi:10.7453/gahmj.2014.068.a

  • Coucke F. Food intolerance in patients with manifest autoimmunity. Observational study. Autoimmun Rev. 2018;17(11):1078-1080. doi: 10.1016/j.autrev.2018.05.011. Epub 2018 Sep 11.
  • 10. Vladimir T et al Higher Plasma Concentration of Food-Specific Antibodies in Persons With Autistic Disorder in Comparison to Their Siblings. Focus Autism Other Dev Disabl 2008; 23: 176-185

  • 4.Atkinson, W et al.

    Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial Gut 2004;53:1459-1464

  • 6. Bentz S, et al. Clinical relevance of IgG antibodies against food antigens in Crohn’s disease: a double-blind cross-over diet intervention study. Digestion. 2010;81:252-64.

  • 2. Dixon H, Treatment of delayed food allergy based on specific immunoglobulin G RAST testing relief. Otoloryngol Head Neck Surg 2000;123:48-54.

  • Aydinlar EI, Dikmen PY, Tiftikci A, et al.

    IgG‐Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome. Headache. 2013;53:514-525. doi:10.1111/j.1526-4610.2012.02296.

  • Zar S, Benson MJ, Kumar D. Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. Am J Gastroenterol. 2005;100(7):1550-1557.
  • Main J, McKenzie H, Yeaman GR, et al. Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease. BMJ. 1988;297(6656):1105-1106. doi:10.1136/bmj.297.6656.1105
  • Mitchell N, Hewitt CE, Jayakody S.

    et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine love headaches. Nutr J. 2011;10, 85 doi:10.1186/1475-2891-10-85

  • 17. Kemeny DM, et al Sub-class of IgG in allergic disease. I. IgG sub-class antibodies in immediate and non-immediate food allergy. Clin Allergy. 1986; 16:571-81.

William Shaw Ph.D

Immunoglobulin G (IgG) food allergy testing has made vast advancements since the year 2003 when the American Academy of Allergy, Asthma, and Immunology published a statement that «Measurement of specific IgG antibodies to foods is also unproven as a diagnostic tool»(1) Most of the IgG food allergy throughout the world is done using the same immunochemical technique.

First, soluble food proteins in solution are reacted to a solid phase that chemically binds to a variety of proteins. The use of plastic microtiter trays with one to several hundred wells has become the most common material used as the solid phase. Then these trays are washed, dried, and stored for later use. A sample of diluted serum is then added to each of the wells. Antibodies of every types in the diluted serum bind to the specific food molecules that are attached to the plastic wells of the tray.

Next, the plates are washed to remove any nonspecific antibodies in the diluted serum. At this time, food antibodies from every of the five major immunoglobulin classes called G, A, M, E, and D may be attached to the food antigens on the plate. The next step confers specificity on the assay. Antisera from sheep, goats, rabbits, or other animals that specifically binds to IgG is added to microtiter wells and only binds to IgG, not to IgA, IgM, IgE, or IgD.

This antibody to IgG has previously been modified by the attachment of an enzyme that can be measured conveniently. The quantity of enzyme bound to food antigen-IgG complexes on the plate is directly related to how much IgG antibody is attached to a given food. The overall technique is termed Enzyme Linked Immuno Assay or ELISA. If IgG4 is measured, an antiserum specific for IgG4 only must be used for the final step.

The clinical usefulness of IgG testing in an array of illnesses is illustrated in an early article published by an otolaryngologist who reported that the majority of his patients had substantial health improvements after an elimination of foods positive by IgG food allergy tests (2).

The overall results demonstrated a 71% success rate for every symptoms achieving at least a 75% improvement level. Of specific interest was the group of patients with chronic, disabling symptoms, unresponsive to other intensive treatments. Whereas 70% obtained 75% or more improvement, 20% of these patients obtained 100% relief. Symptoms most commonly improved 75%-100% on the elimination diets included asthma, coughing, ringing in the ears, chronic fatigue, every types of headaches, gas, bloating, diarrhea, skin rash and itching, and nasal congestion.

The most common IgG food allergies were cow’s milk, garlic, mustard, egg yolk, tea, and chocolate.

The usefulness of IgG food allergy to design customized elimination diets has now been documented in scientific studies. Irritable bowel syndrome (IBS) is a common, costly, and potentially disabling gastrointestinal (GI) disorder characterized by abdominal pain/discomfort with altered bowel habits (e.g., diarrhea, constipation). The major symptoms of IBS are (1) abnormality of bowel movement, (2) reduction in bowel sensitivity thresholds, and (3) psychological abnormality.

Numerous IBS patients own psychological symptoms including depression, anxiety, tension, insomnia, frustration, hypochondria. psychosocial factors (3). Atkinson et al (4)evaluated a entire of 150 outpatients with irritable bowel syndrome (IBS) who were randomized to get, for three months, either a diet excluding every foods to which they had raised IgG antibodies (ELISA test) or a sham diet excluding the same number of foods but not those to which they had antibodies .

What is an igg food allergy test

Patients on the diet dictated by IgG testing had significantly less symptoms than those on the sham diet after 120 days on the diets. Patients who adhered closely to the diet had a marked improvement in symptoms while those with moderate or low adherence to the IgG test dictated diets had poorer response. Similar results were also obtained by Drisko et al (5). They used both elimination diet and probiotic treatment in an open label study of 20 patients with irritable bowel syndrome diagnosed at a medical school gastroenterology department. The most frequent positive serologic IgG antigen-antibody complexes found on the food IgG tests were: baker’s yeast, 17 out of 20 (85%); onion stir, 13 out of 20 (65%); pork, 12 out of 20 (60%); peanut 12 out of 20 (60%); corn, 11 out of 20 (55%);wheat, 10 out of 20 (50%); soybean, 10 (50%); carrot, 9 out of 20 (45%); cheddar cheese, 8 out of 20 (40%); egg white, 8 out of 20 (40%).

Only 5 out of 20 reacted by IgG antibody production to dairy; however the majority of patients reported eliminating dairy prior to trial enrollment presumably clearing antigen-antibody complexes prior to testing. Significant improvements were seen in stool frequency, pain, and IBS quality of life scores. Imbalances of beneficial flora and dysbiotic flora were identified in 100% of subjects by comprehensive stool analysis. There was a trend to improvement of beneficial flora after treatment but no change in dysbiotic flora.

The one-year follow up demonstrated significant continued adherence to the food rotation diet, minimal symptomatic problems with IBS, and perception of control over IBS. The continued use of probiotics was considered less helpful.

IgG food allergy testing was also proved effective in the gastrointestinal disorder Crohn’s disease. Bentz et al (6) found that an elimination diet dictated by IgG food allergy testing resulted in a marked reduction of stool frequency in a double blind cross-over study in which the IgG-dictated diet was compared to a sham diet in 40 patients with Crohn’s disease. IgG food allergies were significantly elevated compared to normal controls.

Cheese and baker’s yeast (Saccharomyces cerevisiae) allergies were extremely common with rates of 83% and 84% respectively. Main et al (7), focusing on the baker’s yeast allergy, also found extremely high prevalence of IgG allergy in patients with Crohn’s disease. Titers of both IgG and IgA to S. cerevisiae in the patients with Crohn’s disease were significantly higher than those in the controls. In contrast, antibody titers in the patients with ulcerative colitis were not significantly diverse from those in the controls. Among the patients with Crohn’s disease there was no significant difference in antibody titers between patients with disease of the little or large bowel.

Since IgG antibodies to S. cerevisiae cross react with Candida albicans (8), Candida species colonization might be a trigger for the development of Crohn’s disease.

IgG food allergy to wheat, gluten, gliadin, rye, and barley are prevalent in the gastrointestinal disorder celiac disease. Virtually every patients with celiac disease own elevated IgG antibodies to gliadin if they currently own wheat or related grains in their diet. The confirmation of celiac disease is confirmed by the presence of flattened mucosa with a lack of villi when a biopsy sample of the little intestine is examined microscopically.

Another confirmation test with equal sensitivity is a blood test for IgA transglutaminase antibodies. The antibody confirmation test is equal in accuracy to the biopsy test with the exception that individuals with IgA deficiency may own untrue negative results. However, I would estimate that only 1% of people with elevated IgG antibodies to gliadin and other grains related to wheat own celiac disease. If the individual is negative for the confirmation tests for celiac disease, numerous patients are frequently erroneously advised that that own no problem with wheat. Hadjivassiliou et al argued that it is a significant clinical error to classify wheat allergy through the filter of celiac disease (9) and argue that celiac disease is a subtype of wheat sensitivity.

Numerous of their patients with wheat allergy but celiac disease negative had remission of severe neurological illnesses when they adopted a gluten free diet and expressed that in these patients the gluten molecule causes an autoimmune reaction in the brain rather than in the intestinal tract, likely against the Purkinje cells that are predominant in the cerebellum.

A wide range of additional studies has proven the clinical worth of IgG antibodies in autism (10), bipolar depression (11), schizophrenia (12), migraine headaches (13), asthma (14), and obesity (15).

Migraine

Migraine has often been attributed to food allergy in numerous studies, 18 but extensive evaluation using IgG antibodies has not been done.

In a recent study, 56 patients with migraine were evaluated for their serum IgG antibodies to 108 diverse food allergens using enzyme immunoassay. When titers were assessed, patients with migraine had elevated IgG levels that were statistically significant when compared to the control group. Researchers also found that elimination diets based upon foods to which patients had elevated IgG levels were successful in controlling symptoms of migraine without pharmaceutical intervention. 19

IgG versus IgE Reactions

Testing for food allergies commonly involves serological tests to detect immunoglobulin G4 (IgG4), which is most likely to develop with exposure to food proteins.

Blood IgG4 is tested against a number of foods using enzyme-linked immunosorbent assay. Testing generally involves exposing the patient’s serum to up to 96 commonly eaten foods and measuring IgG4 and IgE antibodies.

The accuracy of IgG antibody testing is, however, an area of contention in the conventional medical community. Because serum samples may show elevated IgG4 results without the patient demonstrating any clinical symptoms, it’s suggested that IgG4 has both protective as well as harmful properties. 11 Detractors point out that IgG4 lacks any histamine-releasing properties and that there are few controlled studies on the diagnostic worth of food-specific IgG4, making it of little worth as a predictor of allergy.

The latest discussion revolves around IgG levels as reflecting immunological tolerance, or repeated exposure to foods 12, 13 and not hypersensitivity.

Besides clinical experience that demonstrates patients improve from elimination and rotation diets based upon IgG antibody testing to specific foods, numerous clinical studies own been done in recent years involving IgG food-related antibodies. Patients with numerous distressing health conditions own experienced significant improvement as a result of specific IgG testing.

Conclusion and Future Directions

Cell size variability testing for food allergies proved to be completely random in every tests, and therefore has no clinical relevance.

The IgG ELISA method proved to be a consistent, reproducible, and specific test for food allergies in this little study. The clinical relevance of these results were not examined in this study. The results presented here verify that IgG ELISA testing is more dependable and consistent than cell size testing for identifying food sensitivities.

In order to further improve clinical practice, future research should protest how endless IgG antibodies remain athletic after food elimination.

Future studies could also assess how endless it takes to resolve physical symptoms after food elimination. In addition, identifying specific disease states exacerbated by IgG food reactivity would assist clinicians identify the patients who would benefit the most from IgG testing.

Food is medicine, in some extremely fundamental ways. Eliminating harmful foods and encouraging healthful, nutritious foods can own a large impact on health.

In order to eliminate foods, precise identification of potentially harmful foods is essential. In this study, we own identified a food allergy test that is specific and reproducible. This can assist clinicians own more confidence in the food allergy test they recommend to patients.

Introduction

The consumption of food should result in oral tolerance in a healthy individual. If tolerance occurs, the person will not develop physical symptoms as a result of ingesting the food. In contrast, food allergies and hypersensitivities result in wide variety of symptoms in otherwise healthy individuals.1,2,3,4

Food allergies or sensitivities are often underreported because numerous people don’t recognize the signs and symptoms of a food allergy and are never tested.

Common food allergy symptoms include diarrhea, constipation, abdominal bloating, gas, rashes (including eczema), tinnitus, nasal congestion, chronic sinus infections, joint pain, and headaches.5,6,7,8 These symptoms are caused by the immune response to the food allergen.

What is an igg food allergy test

This immune response is measured by looking at antibodies made to specific foods, either directly or indirectly. Food antigens may elicit diverse classes of antibodies, designated as IgM, IgA IgE, and IgG (subtypes). These antibodies may trigger diverse adverse reactions depending on the person.

The greater medical community examines classic food allergies through identification of an IgE response to food antigens. When an allergenic food is ingested, it is taken up by antigen-presenting cells in the Peyer’s patches of the intestine. CD4 T cells specific for the food make Th2 cytokines (IL-4, IL-5, and IL-13), causing B cells specific for the food allergen to make IgE (from IL-4) or secretory IgA (sIgA from IL-5).

IgG antibodies may also be made in response to food allergens. IgE antibodies attach to Fc receptors on mast cells and eosinophils. When these cells encounter triggering foods, they degranulate, which may include the release of histamine. It is this degranulation that causes the more severe allergic reactions such as hives, diarrhea, and anaphylaxis.9

Food hypersensitivity is common, but the symptoms may be hard to distinguish from other chronic diseases or conditions.

Food hypersensitivity is common, but the symptoms may be hard to distinguish from other chronic diseases or conditions.

In contrast to an IgE allergic response which is faster and more severe, food hypersensitivity is a delayed type cell-mediated response. It often is confused with other chronic diseases or conditions. Delayed type hypersensitivity (DTH) responses start when ingested food is taken up by antigen-presenting cells and presented to CD4 T cells that make Th1 cytokines (IFNg, TNFa, and TNFb). B cells specific for the food antigen reply by class switching to IgG3. In DTH reactions, the macrophages, basophils, and CD8 T cells are responsible for the symptoms rather than the antibodies. The cell-mediated response causes the production of reactive oxygen species, prostaglandins, and leukotrienes, leading to a variety of symptoms in the body.

This increases overall inflammation, and therefore can be confused with other diseases that own inflammatory components.10

Researchers are working to understand the significance of subclasses of IgG during allergic response. IgG1 (induced by TNFa) is found in high levels during infectious disease but is also found in allergic or atopic people.11,12 Polysaccharide antigens (usually from bacteria or food) stimulate IgG2.13 IgG3 (induced by IFNg and TNFa) is most often elevated during infectious disease. IgG3 is at lower levels in people with allergies and higher levels in people with DTH.

Elevated IgG4 antibodies own been found in patients with atopic dermatitis and eczema.14 IgG4 is thought to be related to prolonged antigen exposure.15 Similar to IgE, IgG4 requires IL-4 and IL-13 for production.16 Another cytokine, IL-10 may induce IgG4 secretion.17 IL-10 may also determine whether B cells continue to produce IgG4 or class switch to IgE.18 Some allergens do not induce an IgG response at all.19

There are reactions to food that are not immune-mediated. These reactions include direct toxic reactions to a food ingredient.

There are some food components to which everyone reacts; for example, food poisoning is a reaction to a toxin (most commonly staph enterotoxin A or staph enterotoxin B) made by bacteria. Numerous people react to monosodium glutamate or other food chemicals that they are unable detoxify. A genetic predisposition can cause susceptible individuals to overreact to a food ingredient, such as histamine contained in foods such as cheeses and smoked meats. Other food components are problematic for people lacking appropriate enzymes, which may lead to lactose intolerance, favism (glucose-6-phosphate deficiency), and other diagnoses.20

IgG Food Antigen Studies in Children

In one study of IgG antibodies to food, 30 overweight children were evaluated against 30 children of normal weight to see if IgG antibodies predisposed them to low-grade inflammation and atherogenesis.

IgG antibodies to foods, C-reactive protein (CRP), and intima media thickness of the carotid arteries were measured. Results showed that the obese children had higher IgG antibodies to foods than the children who were of normal weight. Researchers concluded that IgG antibodies were associated with systemic inflammation, suggesting the possibility that obesity and atherosclerosis were associated with IgG food antibodies. 16

To determine whether delayed hypersensitivity reaction to foods might be a factor in the development of chronic diarrhea in children, researchers measured IgG antibodies and prescribed an elimination diet to children in 4 diverse groups.

IgG levels were highest for milk and lowest for pork in each of the study cohorts. Symptoms improved for 65 of the 82 children within 1 week to 3 months of dietary intervention. It was concluded that food allergy was a major factor in the development of chronic diarrhea in children, with food-specific IgG assessment an significant component of early management. 17

IgG Allergy Testing

| Lauren Russel, ND, and Leah Alvarado-Paz, ND

Published in: Townsend Letter

By Lauren Russel, ND, and Leah Alvarado-Paz, ND

There is no question that the foods people eat own a large impact on their health and quality of life.

The discussion about adverse food reactions and the health problems associated with them has grown in quality and intensity over the final several decades. From some of our earliest concerns about the impact of cholesterol and fats on health, interest has expanded to include food allergies, propelled forward by the clinical ecology movement. 1

Food allergies are becoming more prevalent in today’s society. It’s estimated that 6% of children and 3-4% of adults may own IgE-mediated food allergies.2, 3 For those with food allergies that are not IgE-mediated and associated with delayed hypersensitivity reactions, estimates are more hard to determine. Some propose that between 45-60% of people may be affected.

4, 5 Food allergies are implicated in a wide variety of conditions, including migraine, irritable bowel syndrome, inflammatory bowel disease, eczema, psoriasis and recurrent infection. 6

Agreement about what constitutes food allergy is clouded, however, by confusion about terminology and there is disagreement on how to define, assess, and diagnose it. 7, 8 Allergy has come to be defined in conventional medical circles as IgE-mediated reactions.

Despite this narrow viewpoint, patients themselves are convinced that foods trigger symptoms. Self-diagnosis of food allergies is common and there is an increasing trend toward diets to address food allergies, including elimination and challenge and rotation diets.

Testing for adverse food reactions serves numerous significant purposes and provides significant benefit to the patient.

Serum testing for food allergies provides a quick response to patients’ questions about food allergies. The written reports given to patients include reference ranges along with instructions to follow in eliminating offending foods. When compliance is high, patients report improvement in symptoms, elimination of long-standing health issues, and, in general, a more satisfying quality of life.

Clinical References

  1. 13.Huber A, et al Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial.

    Int Arch Allergy Immunol. 1998; 115:67-72.

  2. 11. Severance EG et al Immune activation by casein dietary antigens in bipolar disorder. Bipolar Disord 2010;12: 834–842

  3. 1. Statement of the AAAAI Work Group Report: Current Approach to the Diagnosis and Management of Adverse Reactions to Foods, October 2003. http://www.aaaai.org/ask-the-expert/usefulness-of-measurements-of-IgG-antibody.aspx (Accessed October 27,2013).

  4. 7.Janice Main, Hamish McKenzie, Grant R Yeaman, Michael A Kerr, Deborah Robson, Christopher R Pennington, David Parratt Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease BMJ 1988;297:1105-1106

  5. 5.

    Drisko J, Bischoff B, Hall M, McCallum R, Treating Irritable Bowel Syndrome with a Food Elimination Diet Followed by Food Challenge and Probiotics. Journal of the American College of Nutrition 2006; 25: 514–522

  6. 16. Marijn van der Neut Kolfschoten, et al Anti-Inflammatory Activity of Human IgG4 Antibodies by Dynamic Fab Arm Exchange. Science 2007;317:1554-1555

  7. 12. Severance EG, et al Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophr Res. 2010;118:240-7.

  8. 6. Bentz S, et al. Clinical relevance of IgG antibodies against food antigens in Crohn’s disease: a double-blind cross-over diet intervention study.

    Digestion. 2010;81:252-64.

  9. 3. Nagisa Sugaya N and Nomura S, Relationship between cognitive appraisals of symptoms and negative mood for subtypes of irritable bowel syndrome. BioPsychoSocial Medicine 2008;2:9-14

  10. 4.Atkinson, W et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial Gut 2004;53:1459-1464

  11. 2. Dixon H, Treatment of delayed food allergy based on specific immunoglobulin G RAST testing relief. Otoloryngol Head Neck Surg 2000;123:48-54.

  12. 10. Vladimir T et al Higher Plasma Concentration of Food-Specific Antibodies in Persons With Autistic Disorder in Comparison to Their Siblings.

    Focus Autism Other Dev Disabl 2008; 23: 176-185

  13. 8. Thomas Schaffer, Stefan Mueller, , Beatrice Flogerzi, , Beatrice Seibold-Schmid,Alain M. Schoepfer, and Candid Seibold Anti-Saccharomyces cerevisiae Mannan Antibodies (ASCA) of Crohn’s Patients Crossreact with Mannan from Other Yeast Strains, and Murine ASCA IgM Can Be Experimentally Induced with Candida albicans Inflamm Bowel Dis 2007;13:1339 –1346

  14. 14.Vance G. et al. Ovalbumin specific immunoglobulin G and subclass responses through the first five years of life in relation to duration of sensitization and the development of asthma.

    Clia Exp Allergy 2004;34:1452-1459

  15. 15.Wilders-Truschnig M et al. IgG Antibodies Against Food Antigens are Correlated with Inflammation and Intima Media Thickness in Obese Juveniles. Exp Clin Endocrinol Diabetes 2008;116:241-5.

  16. 9. M Hadjivassiliou, R A Grünewald, G A B Davies-Jones Gluten sensitivity as a neurological illness. Neurol Neurosurg Psychiatry 2002;72:560–563

  17. 17.

    Kemeny DM, et al Sub-class of IgG in allergic disease. I. IgG sub-class antibodies in immediate and non-immediate food allergy. Clin Allergy. 1986; 16:571-81.

Types of Hypersensitivity Reactions

A food allergy is an abnormal response to a food protein triggered by the immune system. The development of food allergies is dependent on a number of factors, including exposure to the allergenic food, the number of times the food is consumed, and the integrity of the gastrointestinal system.

Specifically, there are four diverse types of reactions that may happen when a person is exposed to an allergen.

Reactions mediated by IgE are referred to as Type I, in which mast cells and basophils release histamine when exposed to an allergen.

This immediate reaction is both serious and potentially life threatening and characteristic of what we ponder of as the typical ‘atopic’ or allergic reaction to IgE-mediated antigens. Symptoms generally associated with IgE-mediated reactions include congestion, angioedema and urticaria, and often require life-long avoidance of the substance in question. Airway constriction may happen during severe anaphylactic reactions when vascular integrity is compromised and is a frequent cause of mortality.

Some allergies are primarily atopic, love hay fever or peanut allergy 9 and confirmed by elevated levels of IgE in serum. In the Multicenter Allergy Study, researchers discovered that IgE antibodies to egg were the earliest to be detected in infancy, followed by antibodies to milk.

Rates of sensitization were highest at infancy, at 10%, decreasing to 3% by age 6. However, inhalant allergy sensitization developed much later, with rates of sensitization increasing with age. Sensitization to inhalant allergens increased from 1.5% at age 1 to 26% by age 6. 10

In Type II hypersensitivity reactions, attachment of the allergen causes antibody-mediated tissue destruction. This reaction is considered “cytotoxic” because it has a direct effect on the integrity of the cell.

Type III reactions are mediated by a mixed group of antibodies, though IgG antibodies are most prevalent.

Immune complexes activate complement, triggering the release of inflammatory cytokines. The resulting inflammatory cascade contributes to numerous undesirable health symptoms, including joint pain, chronic headaches, fatigue, eczema, and psoriasis, numerous of which are associated with food allergy. Type III reactions are considered to be “delayed” because of the time required to form the immune complexes. Symptoms of exposure may develop numerous hours to days later and make diagnosis of a food-related allergy extremely challenging.

The final type of hypersensitivity reaction is Type IV, in which killer T-cells become cytotoxic when activated by an antigen.

These cytotoxic cells target bacteria, viruses, tumor cells, or other cells of the body. Type IV reactions may also be involved in some delayed hypersensitivity reactions, such as celiac disease, in which there is a reaction to the gliadin part of grains and wheat gluten. Type IV reactions may cause damage to the mucosal lining of the gut or contribute to other protein wasting conditions, love celiac disease, ulcerative colitis, Crohn’s disease, and leaky gut.

Food Allergy Testing

Allergy serum and bloodspot tests measure entire IgG through ELISA/EIA, which includes every the subclasses of IgG.

Sera is added to a 96-well plate containing diverse food antigens and then evaluated for classic antigen/antibody interactions. Precise testing requires the patient to eat a wide range of foods within 3 weeks of assessment for IgG exposure to be present. The test provides a report of whether the levels of antibody to the various foods propose that each one is “safe” to eat, best to eat in moderation, or to avoid entirely.

Other types of testing, such as skin tests, which are dependable for the detection of IgE to environmental allergens, are not dependable for the detection of food allergies.

A further refinement in food allergy testing is the development of the bloodspot test, which requires only a tiny quantity of blood for testing of 45-95 food antigens.

The patient pricks a finger with a lancet and then places drops of blood on a blood spot collection card. The card is air-dried and returned to the laboratory for assessment of IgG4 antibodies to food via ELISA assay. IgG4 results are ranked according to their concentrations in the blood and then ranked according to those results, such as safe, moderately safe, or avoid. These results can then be used to design therapeutic elimination or rotation diets.

IgG Antibodies Detectible Before IgE

IgG antibodies to food are often detectible before IgE antibodies are elevated for common allergic inhalants in children who appear at first to be non-atopic. In a cross-sectional prospective study of the relationship between IgG in foods and IgE in known allergens, researchers found that, when IgG levels were measured in 120 atopic and 144 non-atopic children, the atopic children had higher IgG levels, particularly for egg white, orange, and milk.

These levels correlated with an increased risk of IgE-mediated allergy to cats, dogs, mites, milk and eggs. 14

Sensitization to foods as an increased risk of sensitization to inhalant allergens has been substantiated in a prospective study of 397 IgE-negative children, ages 1-5. Children who were initially IgE-negative for antibodies to mites, dogs and cats were assessed for IgG antibodies to foods. Two years later, 12.8% of the children showed IgE sensitization to dog, cat or mite antibodies along with increased IgG antibody levels for a combination of wheat-rice or orange. It was concluded that elevated levels of IgG to orange and wheat-rice, along with other factors, increased the risk of IgE-mediated allergies to inhalants.

15

In recent years, clinical studies demonstrating that IgG antibody testing is an effective and dependable testing method own been conducted in children and in patients with migraine, irritable bowel syndrome (IBS), and gluten sensitivity.

Design and Methods

Design overview

Blood draws were performed with the same donor for 3 diverse evaluations: 1) within test repeatability for 2 diverse diagnostic tests on a single sample, 2) within participant repeatability over time, and 3) interlaboratory reliability between diagnostic food allergy testing methods (see Figure 1).

Blood collection

Blood was collected using collection tubes or strips provided by each allergy testing company used in the study.

The companies use diverse methods to determine allergic reactions. Alcat (hereafter referred to as cell size variability method) in Deerfield Beach, FL, uses an assay that measures cell size. US Biotek (hereafter referred to as the IgG ELISA method) in Seattle, WA, uses an assay that measures antibody (IgG) concentration.

For the cell size assay, blood was collected into 2 blue-top vials provided (3.8% sodium citrate, 4.5 ml draw).

Blood was shipped overnight at room temperature. Peripheral blood collected for the IgG antibody assay was collected on filter paper strips from a finger stick using a lancet. Blood was allowed to dry on the filter strips at room temperature and shipped via the US Postal Service.

Cell size testing

Cell size variability is measured to determine reactivity to food antigens. Cells from the blood sample are incubated with potential food allergens.

If the individual is sensitive to the food, the cell size changes, most likely due to activation or degranulation. A modified Coulter counter is used to measure cell size.

Antibody testing (ELISA)

Antibody (IgG) specific for a food allergen is measured via ELISA. Food antigens are bound to the surface of an ELISA plate and an individual’s whole blood is added. If the individual has antibodies to the food, the antibodies will bind to the antigen. These antibodies can then be detected with an enzymatic or colorimetric reaction.

Within test repeatability

The first part of the protocol was designed to assess repeatability within a testing method as a measure of reliability and reproducibility.

Blood was collected from the same donor for every time points. On day 1, the several tubes of blood were collected during the same blood draw; the tubes were blinded and sent to both companies for analysis (see Figure 1).

Within participant repeatability over time

Two days after the initial draw (day 2), 2 blood samples were collected during the same blood draw. The tubes were blinded and sent to both companies for analysis.

The next day (day 3), 2 tubes of blood were collected during the same blood draw. The tubes were coded and sent to both companies for analysis. The samples from days 1, 2, and 3 were compared to see if results were consistent over the course of 4 days. A coefficient of variance (CV) and an intraclass correlation coefficient (ICC) were calculated for each test methodology. For the ICC, a worth approaching 1 confirms consistency between the samples. Results were compared between companies in order to determine interlaboratory correlation.

Conclusion

While the mechanism associated with IgG-mediated food allergy may as yet be unknown, the results achieved from serum IgG assessment are extremely clear and provide a valuable means of designing effective treatments.


Total IgG Versus IgG4 Food Allergy

Immunoglobulin G (IgG) is classified into several subclasses termed 1, 2, 3, and 4.

IgGs are composed of two heavy chain–light chain pairs (half-molecules), which are connected via inter–heavy chain disulfide bonds situated in the hinge region (Figure 1). IgG4 antibodies generally represent less than 6% of the entire IgG antibodies. IgG4 antibodies differ functionally from other IgG subclasses in their lack of inflammatory activity, which includes a poor ability to induce complement and immune cell activation because of low affinity for C1q (the q fragment of the first component of complement). Consequently, IgG4 has become the preferred subclass for immunotherapy, in which IgG4 antibodies to antigens are increased to reduce severe antigen reactions mediated by IgE.

If antigens preferentially react with IgG4 antibodies, the antigens cannot react with IgE antibodies that might cause anaphylaxis or other severe reactions. Thus, IgG4 antibodies are often termed blocking antibodies. Another property of blood-derived IgG4 is its inability to cross-link identical antigens, which is referred to as «functional monovalency». IgG4 antibodies are dynamic molecules that exchange half of the antibody molecule specific for one antigen with a heavy-light chain pair from another molecule specific for a diverse antigen, resulting in bi-specific antibodies that are unable to form large cross-linked antibodies that bind complement and thus cause subsequent inflammation(16).

In specific immunotherapy with allergen in allergic rhinitis, for example, increases in allergen-specific IgG4 levels indeed correlate with improved clinical responses. IgG4 antibodies not only block IgE mediated food allergies but also block the reactions of food antigens with other IgG subclasses, reducing inflammatory reactions caused by the other IgG subclasses of antibodies to food antigens.

In IgG mediated food allergy testing, the goal is to identify foods that are capable of causing inflammation that can trigger a large number of adverse reactions. IgG1, IgG2, and IgG3 every are capable of causing inflammation because these antibodies do not exchange heavy and light chains with other antibodies to form bispecific antibodies.

Thus, IgG1, IgG2, and IgG3 antibodies to food antigens can and do form large immune complexes or lattices that repair complement and increase inflammation. The presence of IgG4 antibodies to food antigens indicates the presence of antibodies to foods that will not generally cause inflammation even though high amounts of these antibodies do indicate the presence of immune reactions against food antigens. Testing only for IgG4 antibodies in foods limits the ability of the clinician to determine those foods that are causing significant clinical reactions that are affecting their patients.

The importance of measuring other subtypes of IgG antibodies is highlighted in an article by Kemeny et al. (17). They found that IgG1 antibodies to gluten were elevated in every 20 patients with celiac disease but none of the patients had elevated IgG4 antibodies to gluten.

Results

Reliability of food allergy testing on a single divide sample.

In this study, blood from 1 person was sent to 2 diverse labs to test for food allergies. On the first day, the blood was divide into 4 samples, and 2 samples were sent to each lab. The 2 samples analyzed by each individual lab were compared for similarity. This allowed us to test the internal reliability of each lab.

The results were reported as no reaction (0), low reaction (1), moderate reaction (2) or high reaction (3). If the food reactivity levels differed between the samples, the difference was calculated and reported in Table 1. The difference between reactivity levels was 0 if a food showed up in the same category in both samples. Cabbage had 1 test reporting a moderate reaction (2), and 1 test reporting a high reaction (3), so the difference in reactivity level was 1 since the results differed by 1 category.

To get a score of 3, 1 sample had a high reaction (3) and 1 sample had no reaction (0).

The company using the cell size variability method tested 50 foods in its food allergy panel. Table 1 demonstrates that only 34% of the foods (17 foods) generated identical results between the divide samples. Twenty-eight percent of the foods (14 foods) differed by 1 reactivity level, 10% of the foods (5 foods) differed by 2 reactivity levels, and 28% of the foods (14 foods) differed by 3 reactivity levels. If this were a dependable test for food allergies, we would expect the majority of the foods tested to own identical results.

In this case, 66% of the foods tested differed by 1 or more reactivity levels. The scatterplot for cell size testing method, Figure 2A, depicts a large variability in the results for the divide sample.

Table 1: This table compares results from a divide sample. The reactivity level differences refer to the percentage of samples that own identical results, or results that are off by a number of categories. For this purpose, no reaction = 0, low = 1, moderate = 2, and high = 3.

The reactivity level difference is calculated by taking the absolute difference between the divide sample scores.

The company using the IgG ELISA method tested 96 foods in its food allergy panel. In contrast to the cell size variability method, 95% of the foods (91 foods) were identical between the divide samples. Five percent of the foods (5 foods) differed by 1 reactivity level. No foods differed by more than one reactivity level between the divide samples. The scatterplot for the IgG ELISA method, figure 2B, has a more linear pattern.

Consistency of food allergy testing over time

On 3 diverse days, samples were collected and sent to both labs to test the consistency of test results over the course of a week.

A entire of 4 time points were compared: 2 samples from Monday, 1 sample from Wednesday, and 1 sample from Thursday. The difference in reactivity levels was recorded as the greatest difference in the 4 time points compared. For example, if lamb had no reaction (0) for 3 time points, and high (3) for 1 time point, it would get a difference in reactivity of 3 (the difference between 0 and 3). If every 4 time points were identical for a food, the difference was scored as 0. If 1 food had a low reaction (1) for 1 time point, moderate reactions (2) for 2 time points and high reaction (3) for 1 time point, the largest difference between reactivity levels was calculated at 2 (the difference between 1 and 3).

As shown in Table 2, 2% of the samples (1 of 50 foods) tested by the cell size variability method yielded identical results over the 4 time points.

Twelve percent (6 foods) differed by 1 reactivity level. Twenty-six percent of foods (13 foods) differed by 2 reactivity levels, and 60% of foods (30 foods) differed by 3 reactivity levels. This means that 60% of the foods had at least 1 sample that scored no reaction at 1 time point and scored high reaction for the same food at a diverse time point during the same week.

What is an igg food allergy test

When comparing every 4 time points, the coefficient of variance for the cell size variability method was calculated to be 0.55, with an ICC of 0.01.

Over the Course of a Week Cell Size Method (# of foods out of 50 tested) IgG ELISA Method (# of foods out of 96 tested)
Identical results 2% (1) 82% (79)
1 reactivity level difference 12% (6)

17% (16)

2 reactivity level difference 26% (13) 1% (1)
3 reactivity level difference 60% (30) 0%
Coefficient of variance (CV) 0.55 0.05
Intraclass correlation coefficient (ICC) 0.01 0.99

Table 2: Results in table 2 show the differences in 4 samples every taken over the course of 4 days.

See Procedure section for more details on the samples taken during 1 week. The reactivity level difference in this table reflects the greatest absolute difference between the 4 samples.

Comparatively, 82% of the foods tested (79 of 96 foods) by the IgG ELISA method produced identical results over the 4 time points. Seventeen percent (16 foods) differed by 1 reactivity level. One percent (1 food) had a reactivity level difference of 2 (one sample, no reaction and three samples, moderate reaction).

There were no foods that differed by 3 reactivity levels over the 4 time points. The coefficient of variance was 0.05 for the IgG ELISA method, with an ICC of 0.99, which demonstrates a much more consistent reactivity pattern.

Celiac Disease and Non-celiac Gluten Sensitivity

No discussion of allergy testing would be finish without addressing gluten sensitivity and gluten intolerance. Celiac disease, also known as gluten-sensitive enteropathy, is a food intolerance that affects individuals with a genetic predisposition to react to gliadin, a gluten protein found in wheat, barley, and rye. While the exact mechanism is unknown, exposure to these proteins causes an inflammatory reaction and increased intestinal permeability 30, 31 leading to symptoms of diarrhea, malabsorption, and irritable bowel syndrome.

Chronic exposure leads to atrophy of the villi of the little intestine. 32 To date, the only effective treatment for celiac disease is a gluten-free diet.

Definitive diagnosis of celiac disease is confirmed through biopsy of the little intestine, with serological testing for anti-gliadin (AGA), IgA and IgG, anti-endomysial (EMA), and anti-tissue transglutaminase (tTG) antibodies conducted as part of the diagnostic evaluation. Serum IgG antibody testing for gluten/gliadin antibodies is done using an FDA-approved ELISA.

Research has shown that gluten sensitivity may, in fact, happen without villous atrophy being apparent.

33, 34 Other tissues may be targeted in gluten-sensitive individuals, manifesting as autoimmune diseases or skin conditions, such as dermatitis herpetiformis. Some own recommended that early diagnosis, using serum anti-gliadin IgG testing before tTG or EMA levels are elevated and before villous atrophy has occurred, can assist identify those who are at risk and prevent progression of the disease through gluten avoidance. 35

There is a large group of people in our population, however, who react to gluten and are “gluten sensitive” and do not own celiac disease.

Clinical evidence suggests that a gluten-free diet in these individuals, based upon serum IgG levels, reduces symptoms and improves health in a vast majority of those assessed. Preliminary studies are now underway to identify the mechanism with which gluten affects the body in those who are gluten sensitive but without identifiable celiac disease. 36

Discussion

An ideal response to food antigen is tolerance. Yet, some patients develop allergic responses to seemingly innocuous food antigens. Clinicians commonly recommend lab testing when a patient has a suspected food allergy. It is possible that some types of food reactivity will show up in 1 type of testing method and not others.

Clinicians and patients rely on the lab tests to be both precise and reproducible. When a physician reported that 2 types of food allergy tests reported diverse results for a single patient, we tested the reliability of food allergy testing for the 2 types of food allergy tests in question. Although both of these labs are Clinical Laboratory Improvement Amendments (CLIA)– certified, certification does not ensure the consistency and reproducibility of laboratory tests.

Before we could examine interlaboratory results of food allergy testing, intralaboratory reliability needed to be evaluated.

Excellent intralaboratory reproducibility means that when a sample is compared with itself (as in a divide sample), the results are expected to be identical. Similarly, when a person maintains a normal dietary routine over the course of a week, the results of a food allergy test would be expected to be the same. In this study, the cell size variability method delivered extremely diverse results for every the samples submitted, and therefore had no internal reproducibility or accuracy.

The IgG ELISA method had excellent intralaboratory correlation for the divide sample and the samples analyzed over the course of a week. The unreliability of the cell size variability method results prevented an interlaboratory analysis comparing the results of the cell size variability method to the IgG ELISA method.

Other researchers own compared allergy testing methods, although most studies focus on IgE-related allergies as opposed to IgG-mediated responses. Double-blind placebo-controlled food challenge (DBPCFC) is considered the gold standard in food allergy testing and is strongly correlated with IgE testing.26,27 In this type of testing, the reaction of a suspected allergenic food is compared to a placebo food, known to not evoke a response.

Foods that are known to induce anaphylaxis are not generally tested. The DBPCFC identifies foods that evoke immediate food allergy symptoms.28 Skin tests can also be used to identify food allergens. These tests are more sensitive than IgE blood tests.29

IgE to food allergens demonstrates an immediate phase immune response. Delayed type responses, however, are not mediated by IgE antibodies and will not show up with this type of testing.30 For symptoms of food allergies caused by delayed type hypersensitivity reactions such as headaches, mood swings, intestinal upset, pain, and attention problems, the DBPCFC or skin tests may present a untrue negative.

In this study, IgG ELISA testing was more reproducible than cell-size testing.

In general ELISA is known to be consistent and is routinely used for scientific testing.31 The sensitivity of ELISA as a method for food allergy testing is dependent upon the food antigen used as well as the quantity of antibody present. IgE food antigens used for ELISA assays own been standardized and are consistent between diverse laboratories. IgG food antigens own not been standardized, which accounts for some of the variation between laboratories. Every commercial food antigens for ELISA testing are made from raw foods (both IgE and IgG antigens).

Cooking food exposes diverse antigens and epitopes which may affect ELISA test results.32 For example, pecans, wheat flour, roasted peanuts, lentils, almonds, cashews, walnuts, soy beans, shrimp, scallop, tuna, egg, apple, plum, milk, and potatoes own been shown to own antigens that differ between raw and cooked forms.33,34 Another researcher suggests that cooked egg (baked egg especially) produces less of a reaction than raw egg.35

The participant of this study had IgG reactions to milk and soy. The most common IgE mediated food allergens in the general population are milk, soy, egg, peanut, wheat, tree nuts (walnuts and cashews), fish, and shellfish.

These foods account for 85% of the commonly recognized food allergens.36 The other foods with high reactions for this participant included almonds, corn, lima beans, bananas, and blueberries. Every of these foods were regularly included in the participant’s diet before the food allergy tests.

Cell size testing as a measure of food reactivity is not well studied in the literature. Consistent with the data reported herein, most studies propose that it is unreliable.37,38,39 The company that performed the cell size variability method was told of the results in a phone call a month after the testing was finish and said that there were no irregularities during that week and that they stood by their results.

While we can hypothesize a mechanism for identifying food allergies from cell size differentials, the data clearly protest this method is not specific, not reproducible, and was not related to food reactions in this participant. As the scientific community continues to understand the importance of the antigen being used and the accuracy of diverse tests in providing relevant clinical guidance, the consistency between laboratories and the method they employ must improve.

Irritable Bowel Syndrome (IBS)

Irritable bowel syndrome (IBS) is a complicated disorder in which patients experience abdominal pain and discomfort with frequent bouts of diarrhea or constipation.

Treatment is challenging and numerous traditional methods used to predict it are disappointing, with diagnosis based on exclusion in most cases. 20 While IBS may own numerous causes, patients remain convinced that dietary intolerance and food sensitivities are at the root of the problem. When certain foods are eliminated from the diet of IBS patients, they improve, making dietary modification through elimination of specific foods and food challenge an effective strategy.

In a extremely clear, double-blind, randomized, controlled study, 131 participants between the ages of 18 and 75 with uncomplicated IBS were enrolled with two outcome measures. The first was to assess what would happen to symptom severity when participants were put on elimination diets based upon their IgG antibodies to foods.

The second objective of the study was to measure changes in symptom severity when foods were reintroduced in the diet. 21

IgG antibodies were measured using an enzyme-linked immunosorbant assay (ELISA) test designed to measure antigens to 29 diverse foods. Patients were assigned to groups to get either a “true” or a “sham” elimination diet based upon detected IgG antibody levels. Symptom severity was assessed for each patient prior to the study, along with atopic status.

On average, most study participants had had symptoms of IBS for 10 years and, on average, had elevated IgG titers to 6-7 foods.

At the finish of the 12-week study, symptom severity decreased by 10% in those on the true diet. While improvement was greatest among participants on the true diet, there was some improvement noted in symptom severity for those on the sham diet, suggesting there was some little placebo effect.

In participants who were fully compliant with the true diet and had the highest level of sensitivity to foods as demonstrated by their IgG titers, there was a 26% improvement in symptom severity. This was not true for participants with high sensitivity who were on the sham diet, however.

When foods with high IgG antibody titers were reintroduced to the diet, symptom severity increased in those on the true diet by 83% and by 31% in the sham group.

22

In another study involving 25 participants with irritable bowel syndrome (IBS), dietary modification was sure following measurement of their IgG4 antibody levels to specific foods. IgG4 antibody levels were assessed for beef, pork, lamb, chicken, fish, shrimp, yeast, tomatoes, peanuts, milk, eggs, cheese, wheat, rice, potatoes, and soybeans and foods with titers over 250 mcg/l were eliminated from the diet for 6 months.

The highest titers were recorded for beef, pork, lamb, eggs, milk, and wheat. When assessed at 6 months, study participants reported reduced pain and pain frequency, reduced bloating, improvement in bowel habits, and improvement in quality of life. 23

More recently, a study comparing IgG, IgE and entire IgE antibody titers was conducted in patients with IBS and functional dyspepsia (FD). Serum IgG and IgE antibody titers were measured for 14 foods, including tomatoes, wheat, crab, codfish, eggs, corn, mushrooms, milk, port, rice, shrimp, beef, chicken and soybeans.

As in similar studies, there were no significant levels of food-specific IgE antigens. However, IgG levels were elevated for crab, egg, shrimp, soybean, and wheat as compared to controls in patients with IBS. In patients with FD, IgG antibodies were significantly higher for egg and soybean. While there were elevations in IgG food-specific antigens, there was no correlation to symptom severity. 24

In yet another study, 108 study participants with IBS were tested for their sensitivity to 16 foods using IgG4 and IgE titers and skin prick testing. Study participants had the highest IgG4 titers to wheat, beef, and lamb, with no significant results reported for potatoes, rice, fish, chicken, yeast, tomato, or shrimp.

In contrast, IgE titers were not elevated in study participants or controls and skin prick testing showed only one positive result in 5 of 56 patients. Researchers concluded that there is a possible pathophysiological basis for the IgG4 antibodies detected in patients with IBS. 25 While the mechanism may not yet be clarified, mucosal inflammation and immunological reactivity appear to be a factor in IBS and deserve further study. 26

Treatment with elimination and rotation diets has also been shown to be effective for IBS patients who are not responsive to other forms of therapy.

In an open label pilot study, 25 patients with diarrhea dominant IBS 27 were first screened for their serum IgG4 and IgE titers, along with mold antigen panels. Every patients had baseline antibody abnormalities and were given elimination diets based upon their antibody levels and asked to follow them for up to 4 weeks. After the elimination phase, foods were challenged and reintroduced in a rotation diet if there were no symptoms. Any food causing symptoms was eliminated from the diet for an additional 6 months.

Study participants were given probiotics for 4 months out of the 6-month trial period.

At the finish of the trial period, patients reported improvement in stool frequency and quality of life scores. Most patients sustained their clinical improvement one year after the trial ended, reporting few symptoms and continued adherence to the rotation diet. 28

Eliminating foods based upon IgG4 levels in patients with IBS has been sure by other researchers to be a extremely valuable treatment modality. 29

Acknowledgements

Helfgott Research Institute provided funding for this study and consulted on the study design.

William Gregory, PhD, provided statistical consultation and comments on the manuscript.

Between Divide Samples Cell Size Method (# of foods out of 50 tested) IgG ELISA Method (# of foods out of 96 tested)
Identical results 34% (17) 95% (91)
1 reactivity level difference 28% (14) 5% (5)
2 reactivity level difference 10% (5) 0%
3 reactivity level difference 28% (14) 0%

William Shaw Ph.D

Immunoglobulin G (IgG) food allergy testing has made vast advancements since the year 2003 when the American Academy of Allergy, Asthma, and Immunology published a statement that «Measurement of specific IgG antibodies to foods is also unproven as a diagnostic tool»(1) Most of the IgG food allergy throughout the world is done using the same immunochemical technique.

First, soluble food proteins in solution are reacted to a solid phase that chemically binds to a variety of proteins. The use of plastic microtiter trays with one to several hundred wells has become the most common material used as the solid phase. Then these trays are washed, dried, and stored for later use. A sample of diluted serum is then added to each of the wells. Antibodies of every types in the diluted serum bind to the specific food molecules that are attached to the plastic wells of the tray. Next, the plates are washed to remove any nonspecific antibodies in the diluted serum.

At this time, food antibodies from every of the five major immunoglobulin classes called G, A, M, E, and D may be attached to the food antigens on the plate. The next step confers specificity on the assay. Antisera from sheep, goats, rabbits, or other animals that specifically binds to IgG is added to microtiter wells and only binds to IgG, not to IgA, IgM, IgE, or IgD. This antibody to IgG has previously been modified by the attachment of an enzyme that can be measured conveniently. The quantity of enzyme bound to food antigen-IgG complexes on the plate is directly related to how much IgG antibody is attached to a given food. The overall technique is termed Enzyme Linked Immuno Assay or ELISA.

If IgG4 is measured, an antiserum specific for IgG4 only must be used for the final step.

The clinical usefulness of IgG testing in an array of illnesses is illustrated in an early article published by an otolaryngologist who reported that the majority of his patients had substantial health improvements after an elimination of foods positive by IgG food allergy tests (2). The overall results demonstrated a 71% success rate for every symptoms achieving at least a 75% improvement level.

Of specific interest was the group of patients with chronic, disabling symptoms, unresponsive to other intensive treatments. Whereas 70% obtained 75% or more improvement, 20% of these patients obtained 100% relief. Symptoms most commonly improved 75%-100% on the elimination diets included asthma, coughing, ringing in the ears, chronic fatigue, every types of headaches, gas, bloating, diarrhea, skin rash and itching, and nasal congestion. The most common IgG food allergies were cow’s milk, garlic, mustard, egg yolk, tea, and chocolate.

The usefulness of IgG food allergy to design customized elimination diets has now been documented in scientific studies.

Irritable bowel syndrome (IBS) is a common, costly, and potentially disabling gastrointestinal (GI) disorder characterized by abdominal pain/discomfort with altered bowel habits (e.g., diarrhea, constipation). The major symptoms of IBS are (1) abnormality of bowel movement, (2) reduction in bowel sensitivity thresholds, and (3) psychological abnormality. Numerous IBS patients own psychological symptoms including depression, anxiety, tension, insomnia, frustration, hypochondria. psychosocial factors (3).

Atkinson et al (4)evaluated a entire of 150 outpatients with irritable bowel syndrome (IBS) who were randomized to get, for three months, either a diet excluding every foods to which they had raised IgG antibodies (ELISA test) or a sham diet excluding the same number of foods but not those to which they had antibodies . Patients on the diet dictated by IgG testing had significantly less symptoms than those on the sham diet after 120 days on the diets. Patients who adhered closely to the diet had a marked improvement in symptoms while those with moderate or low adherence to the IgG test dictated diets had poorer response.

Similar results were also obtained by Drisko et al (5). They used both elimination diet and probiotic treatment in an open label study of 20 patients with irritable bowel syndrome diagnosed at a medical school gastroenterology department. The most frequent positive serologic IgG antigen-antibody complexes found on the food IgG tests were: baker’s yeast, 17 out of 20 (85%); onion stir, 13 out of 20 (65%); pork, 12 out of 20 (60%); peanut 12 out of 20 (60%); corn, 11 out of 20 (55%);wheat, 10 out of 20 (50%); soybean, 10 (50%); carrot, 9 out of 20 (45%); cheddar cheese, 8 out of 20 (40%); egg white, 8 out of 20 (40%). Only 5 out of 20 reacted by IgG antibody production to dairy; however the majority of patients reported eliminating dairy prior to trial enrollment presumably clearing antigen-antibody complexes prior to testing.

Significant improvements were seen in stool frequency, pain, and IBS quality of life scores. Imbalances of beneficial flora and dysbiotic flora were identified in 100% of subjects by comprehensive stool analysis. There was a trend to improvement of beneficial flora after treatment but no change in dysbiotic flora. The one-year follow up demonstrated significant continued adherence to the food rotation diet, minimal symptomatic problems with IBS, and perception of control over IBS.

The continued use of probiotics was considered less helpful.

IgG food allergy testing was also proved effective in the gastrointestinal disorder Crohn’s disease. Bentz et al (6) found that an elimination diet dictated by IgG food allergy testing resulted in a marked reduction of stool frequency in a double blind cross-over study in which the IgG-dictated diet was compared to a sham diet in 40 patients with Crohn’s disease. IgG food allergies were significantly elevated compared to normal controls. Cheese and baker’s yeast (Saccharomyces cerevisiae) allergies were extremely common with rates of 83% and 84% respectively. Main et al (7), focusing on the baker’s yeast allergy, also found extremely high prevalence of IgG allergy in patients with Crohn’s disease.

Titers of both IgG and IgA to S. cerevisiae in the patients with Crohn’s disease were significantly higher than those in the controls. In contrast, antibody titers in the patients with ulcerative colitis were not significantly diverse from those in the controls. Among the patients with Crohn’s disease there was no significant difference in antibody titers between patients with disease of the little or large bowel. Since IgG antibodies to S. cerevisiae cross react with Candida albicans (8), Candida species colonization might be a trigger for the development of Crohn’s disease.

IgG food allergy to wheat, gluten, gliadin, rye, and barley are prevalent in the gastrointestinal disorder celiac disease.

Virtually every patients with celiac disease own elevated IgG antibodies to gliadin if they currently own wheat or related grains in their diet. The confirmation of celiac disease is confirmed by the presence of flattened mucosa with a lack of villi when a biopsy sample of the little intestine is examined microscopically. Another confirmation test with equal sensitivity is a blood test for IgA transglutaminase antibodies. The antibody confirmation test is equal in accuracy to the biopsy test with the exception that individuals with IgA deficiency may own untrue negative results. However, I would estimate that only 1% of people with elevated IgG antibodies to gliadin and other grains related to wheat own celiac disease.

If the individual is negative for the confirmation tests for celiac disease, numerous patients are frequently erroneously advised that that own no problem with wheat. Hadjivassiliou et al argued that it is a significant clinical error to classify wheat allergy through the filter of celiac disease (9) and argue that celiac disease is a subtype of wheat sensitivity. Numerous of their patients with wheat allergy but celiac disease negative had remission of severe neurological illnesses when they adopted a gluten free diet and expressed that in these patients the gluten molecule causes an autoimmune reaction in the brain rather than in the intestinal tract, likely against the Purkinje cells that are predominant in the cerebellum.

A wide range of additional studies has proven the clinical worth of IgG antibodies in autism (10), bipolar depression (11), schizophrenia (12), migraine headaches (13), asthma (14), and obesity (15).

Migraine

Migraine has often been attributed to food allergy in numerous studies, 18 but extensive evaluation using IgG antibodies has not been done.

In a recent study, 56 patients with migraine were evaluated for their serum IgG antibodies to 108 diverse food allergens using enzyme immunoassay. When titers were assessed, patients with migraine had elevated IgG levels that were statistically significant when compared to the control group. Researchers also found that elimination diets based upon foods to which patients had elevated IgG levels were successful in controlling symptoms of migraine without pharmaceutical intervention.

19

IgG versus IgE Reactions

Testing for food allergies commonly involves serological tests to detect immunoglobulin G4 (IgG4), which is most likely to develop with exposure to food proteins. Blood IgG4 is tested against a number of foods using enzyme-linked immunosorbent assay. Testing generally involves exposing the patient’s serum to up to 96 commonly eaten foods and measuring IgG4 and IgE antibodies.

The accuracy of IgG antibody testing is, however, an area of contention in the conventional medical community.

Because serum samples may show elevated IgG4 results without the patient demonstrating any clinical symptoms, it’s suggested that IgG4 has both protective as well as harmful properties. 11 Detractors point out that IgG4 lacks any histamine-releasing properties and that there are few controlled studies on the diagnostic worth of food-specific IgG4, making it of little worth as a predictor of allergy. The latest discussion revolves around IgG levels as reflecting immunological tolerance, or repeated exposure to foods 12, 13 and not hypersensitivity.

Besides clinical experience that demonstrates patients improve from elimination and rotation diets based upon IgG antibody testing to specific foods, numerous clinical studies own been done in recent years involving IgG food-related antibodies.

Patients with numerous distressing health conditions own experienced significant improvement as a result of specific IgG testing.

Conclusion and Future Directions

Cell size variability testing for food allergies proved to be completely random in every tests, and therefore has no clinical relevance. The IgG ELISA method proved to be a consistent, reproducible, and specific test for food allergies in this little study. The clinical relevance of these results were not examined in this study.

The results presented here verify that IgG ELISA testing is more dependable and consistent than cell size testing for identifying food sensitivities.

In order to further improve clinical practice, future research should protest how endless IgG antibodies remain athletic after food elimination. Future studies could also assess how endless it takes to resolve physical symptoms after food elimination. In addition, identifying specific disease states exacerbated by IgG food reactivity would assist clinicians identify the patients who would benefit the most from IgG testing.

Food is medicine, in some extremely fundamental ways.

Eliminating harmful foods and encouraging healthful, nutritious foods can own a large impact on health. In order to eliminate foods, precise identification of potentially harmful foods is essential. In this study, we own identified a food allergy test that is specific and reproducible. This can assist clinicians own more confidence in the food allergy test they recommend to patients.

Introduction

The consumption of food should result in oral tolerance in a healthy individual. If tolerance occurs, the person will not develop physical symptoms as a result of ingesting the food.

In contrast, food allergies and hypersensitivities result in wide variety of symptoms in otherwise healthy individuals.1,2,3,4

Food allergies or sensitivities are often underreported because numerous people don’t recognize the signs and symptoms of a food allergy and are never tested. Common food allergy symptoms include diarrhea, constipation, abdominal bloating, gas, rashes (including eczema), tinnitus, nasal congestion, chronic sinus infections, joint pain, and headaches.5,6,7,8 These symptoms are caused by the immune response to the food allergen.

This immune response is measured by looking at antibodies made to specific foods, either directly or indirectly. Food antigens may elicit diverse classes of antibodies, designated as IgM, IgA IgE, and IgG (subtypes). These antibodies may trigger diverse adverse reactions depending on the person.

The greater medical community examines classic food allergies through identification of an IgE response to food antigens. When an allergenic food is ingested, it is taken up by antigen-presenting cells in the Peyer’s patches of the intestine. CD4 T cells specific for the food make Th2 cytokines (IL-4, IL-5, and IL-13), causing B cells specific for the food allergen to make IgE (from IL-4) or secretory IgA (sIgA from IL-5).

IgG antibodies may also be made in response to food allergens. IgE antibodies attach to Fc receptors on mast cells and eosinophils. When these cells encounter triggering foods, they degranulate, which may include the release of histamine. It is this degranulation that causes the more severe allergic reactions such as hives, diarrhea, and anaphylaxis.9

Food hypersensitivity is common, but the symptoms may be hard to distinguish from other chronic diseases or conditions.

Food hypersensitivity is common, but the symptoms may be hard to distinguish from other chronic diseases or conditions.

In contrast to an IgE allergic response which is faster and more severe, food hypersensitivity is a delayed type cell-mediated response. It often is confused with other chronic diseases or conditions. Delayed type hypersensitivity (DTH) responses start when ingested food is taken up by antigen-presenting cells and presented to CD4 T cells that make Th1 cytokines (IFNg, TNFa, and TNFb). B cells specific for the food antigen reply by class switching to IgG3. In DTH reactions, the macrophages, basophils, and CD8 T cells are responsible for the symptoms rather than the antibodies.

The cell-mediated response causes the production of reactive oxygen species, prostaglandins, and leukotrienes, leading to a variety of symptoms in the body. This increases overall inflammation, and therefore can be confused with other diseases that own inflammatory components.10

Researchers are working to understand the significance of subclasses of IgG during allergic response. IgG1 (induced by TNFa) is found in high levels during infectious disease but is also found in allergic or atopic people.11,12 Polysaccharide antigens (usually from bacteria or food) stimulate IgG2.13 IgG3 (induced by IFNg and TNFa) is most often elevated during infectious disease.

IgG3 is at lower levels in people with allergies and higher levels in people with DTH. Elevated IgG4 antibodies own been found in patients with atopic dermatitis and eczema.14 IgG4 is thought to be related to prolonged antigen exposure.15 Similar to IgE, IgG4 requires IL-4 and IL-13 for production.16 Another cytokine, IL-10 may induce IgG4 secretion.17 IL-10 may also determine whether B cells continue to produce IgG4 or class switch to IgE.18 Some allergens do not induce an IgG response at all.19

There are reactions to food that are not immune-mediated. These reactions include direct toxic reactions to a food ingredient.

There are some food components to which everyone reacts; for example, food poisoning is a reaction to a toxin (most commonly staph enterotoxin A or staph enterotoxin B) made by bacteria. Numerous people react to monosodium glutamate or other food chemicals that they are unable detoxify. A genetic predisposition can cause susceptible individuals to overreact to a food ingredient, such as histamine contained in foods such as cheeses and smoked meats. Other food components are problematic for people lacking appropriate enzymes, which may lead to lactose intolerance, favism (glucose-6-phosphate deficiency), and other diagnoses.20

IgG Food Antigen Studies in Children

In one study of IgG antibodies to food, 30 overweight children were evaluated against 30 children of normal weight to see if IgG antibodies predisposed them to low-grade inflammation and atherogenesis.

IgG antibodies to foods, C-reactive protein (CRP), and intima media thickness of the carotid arteries were measured. Results showed that the obese children had higher IgG antibodies to foods than the children who were of normal weight. Researchers concluded that IgG antibodies were associated with systemic inflammation, suggesting the possibility that obesity and atherosclerosis were associated with IgG food antibodies. 16

To determine whether delayed hypersensitivity reaction to foods might be a factor in the development of chronic diarrhea in children, researchers measured IgG antibodies and prescribed an elimination diet to children in 4 diverse groups. IgG levels were highest for milk and lowest for pork in each of the study cohorts.

Symptoms improved for 65 of the 82 children within 1 week to 3 months of dietary intervention. It was concluded that food allergy was a major factor in the development of chronic diarrhea in children, with food-specific IgG assessment an significant component of early management. 17

IgG Allergy Testing

| Lauren Russel, ND, and Leah Alvarado-Paz, ND

Published in: Townsend Letter

By Lauren Russel, ND, and Leah Alvarado-Paz, ND

There is no question that the foods people eat own a large impact on their health and quality of life.

The discussion about adverse food reactions and the health problems associated with them has grown in quality and intensity over the final several decades. From some of our earliest concerns about the impact of cholesterol and fats on health, interest has expanded to include food allergies, propelled forward by the clinical ecology movement. 1

Food allergies are becoming more prevalent in today’s society.

It’s estimated that 6% of children and 3-4% of adults may own IgE-mediated food allergies.2, 3 For those with food allergies that are not IgE-mediated and associated with delayed hypersensitivity reactions, estimates are more hard to determine. Some propose that between 45-60% of people may be affected. 4, 5 Food allergies are implicated in a wide variety of conditions, including migraine, irritable bowel syndrome, inflammatory bowel disease, eczema, psoriasis and recurrent infection.

6

Agreement about what constitutes food allergy is clouded, however, by confusion about terminology and there is disagreement on how to define, assess, and diagnose it. 7, 8 Allergy has come to be defined in conventional medical circles as IgE-mediated reactions.

Despite this narrow viewpoint, patients themselves are convinced that foods trigger symptoms. Self-diagnosis of food allergies is common and there is an increasing trend toward diets to address food allergies, including elimination and challenge and rotation diets.

Testing for adverse food reactions serves numerous significant purposes and provides significant benefit to the patient.

Serum testing for food allergies provides a quick response to patients’ questions about food allergies. The written reports given to patients include reference ranges along with instructions to follow in eliminating offending foods. When compliance is high, patients report improvement in symptoms, elimination of long-standing health issues, and, in general, a more satisfying quality of life.

Clinical References

  1. 13.Huber A, et al Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial.

    Int Arch Allergy Immunol. 1998; 115:67-72.

  2. 11. Severance EG et al Immune activation by casein dietary antigens in bipolar disorder. Bipolar Disord 2010;12: 834–842

  3. 1. Statement of the AAAAI Work Group Report: Current Approach to the Diagnosis and Management of Adverse Reactions to Foods, October 2003. http://www.aaaai.org/ask-the-expert/usefulness-of-measurements-of-IgG-antibody.aspx (Accessed October 27,2013).

  4. 7.Janice Main, Hamish McKenzie, Grant R Yeaman, Michael A Kerr, Deborah Robson, Christopher R Pennington, David Parratt Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease BMJ 1988;297:1105-1106

  5. 5.

    Drisko J, Bischoff B, Hall M, McCallum R, Treating Irritable Bowel Syndrome with a Food Elimination Diet Followed by Food Challenge and Probiotics. Journal of the American College of Nutrition 2006; 25: 514–522

  6. 16. Marijn van der Neut Kolfschoten, et al Anti-Inflammatory Activity of Human IgG4 Antibodies by Dynamic Fab Arm Exchange. Science 2007;317:1554-1555

  7. 12. Severance EG, et al Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophr Res. 2010;118:240-7.

  8. 6. Bentz S, et al. Clinical relevance of IgG antibodies against food antigens in Crohn’s disease: a double-blind cross-over diet intervention study.

    Digestion. 2010;81:252-64.

  9. 3. Nagisa Sugaya N and Nomura S, Relationship between cognitive appraisals of symptoms and negative mood for subtypes of irritable bowel syndrome. BioPsychoSocial Medicine 2008;2:9-14

  10. 4.Atkinson, W et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial Gut 2004;53:1459-1464

  11. 2. Dixon H, Treatment of delayed food allergy based on specific immunoglobulin G RAST testing relief. Otoloryngol Head Neck Surg 2000;123:48-54.

  12. 10. Vladimir T et al Higher Plasma Concentration of Food-Specific Antibodies in Persons With Autistic Disorder in Comparison to Their Siblings.

    Focus Autism Other Dev Disabl 2008; 23: 176-185

  13. 8. Thomas Schaffer, Stefan Mueller, , Beatrice Flogerzi, , Beatrice Seibold-Schmid,Alain M. Schoepfer, and Candid Seibold Anti-Saccharomyces cerevisiae Mannan Antibodies (ASCA) of Crohn’s Patients Crossreact with Mannan from Other Yeast Strains, and Murine ASCA IgM Can Be Experimentally Induced with Candida albicans Inflamm Bowel Dis 2007;13:1339 –1346

  14. 14.Vance G. et al. Ovalbumin specific immunoglobulin G and subclass responses through the first five years of life in relation to duration of sensitization and the development of asthma. Clia Exp Allergy 2004;34:1452-1459

  15. 15.Wilders-Truschnig M et al.

    IgG Antibodies Against Food Antigens are Correlated with Inflammation and Intima Media Thickness in Obese Juveniles. Exp Clin Endocrinol Diabetes 2008;116:241-5.

  16. 9. M Hadjivassiliou, R A Grünewald, G A B Davies-Jones Gluten sensitivity as a neurological illness. Neurol Neurosurg Psychiatry 2002;72:560–563

  17. 17. Kemeny DM, et al Sub-class of IgG in allergic disease. I. IgG sub-class antibodies in immediate and non-immediate food allergy. Clin Allergy.

    1986; 16:571-81.

Types of Hypersensitivity Reactions

A food allergy is an abnormal response to a food protein triggered by the immune system. The development of food allergies is dependent on a number of factors, including exposure to the allergenic food, the number of times the food is consumed, and the integrity of the gastrointestinal system.

Specifically, there are four diverse types of reactions that may happen when a person is exposed to an allergen.

Reactions mediated by IgE are referred to as Type I, in which mast cells and basophils release histamine when exposed to an allergen.

What is an igg food allergy test

This immediate reaction is both serious and potentially life threatening and characteristic of what we ponder of as the typical ‘atopic’ or allergic reaction to IgE-mediated antigens. Symptoms generally associated with IgE-mediated reactions include congestion, angioedema and urticaria, and often require life-long avoidance of the substance in question. Airway constriction may happen during severe anaphylactic reactions when vascular integrity is compromised and is a frequent cause of mortality.

Some allergies are primarily atopic, love hay fever or peanut allergy 9 and confirmed by elevated levels of IgE in serum. In the Multicenter Allergy Study, researchers discovered that IgE antibodies to egg were the earliest to be detected in infancy, followed by antibodies to milk.

Rates of sensitization were highest at infancy, at 10%, decreasing to 3% by age 6. However, inhalant allergy sensitization developed much later, with rates of sensitization increasing with age. Sensitization to inhalant allergens increased from 1.5% at age 1 to 26% by age 6. 10

In Type II hypersensitivity reactions, attachment of the allergen causes antibody-mediated tissue destruction. This reaction is considered “cytotoxic” because it has a direct effect on the integrity of the cell.

Type III reactions are mediated by a mixed group of antibodies, though IgG antibodies are most prevalent. Immune complexes activate complement, triggering the release of inflammatory cytokines.

The resulting inflammatory cascade contributes to numerous undesirable health symptoms, including joint pain, chronic headaches, fatigue, eczema, and psoriasis, numerous of which are associated with food allergy. Type III reactions are considered to be “delayed” because of the time required to form the immune complexes. Symptoms of exposure may develop numerous hours to days later and make diagnosis of a food-related allergy extremely challenging.

The final type of hypersensitivity reaction is Type IV, in which killer T-cells become cytotoxic when activated by an antigen. These cytotoxic cells target bacteria, viruses, tumor cells, or other cells of the body.

Type IV reactions may also be involved in some delayed hypersensitivity reactions, such as celiac disease, in which there is a reaction to the gliadin part of grains and wheat gluten. Type IV reactions may cause damage to the mucosal lining of the gut or contribute to other protein wasting conditions, love celiac disease, ulcerative colitis, Crohn’s disease, and leaky gut.

Food Allergy Testing

Allergy serum and bloodspot tests measure entire IgG through ELISA/EIA, which includes every the subclasses of IgG. Sera is added to a 96-well plate containing diverse food antigens and then evaluated for classic antigen/antibody interactions.

Precise testing requires the patient to eat a wide range of foods within 3 weeks of assessment for IgG exposure to be present. The test provides a report of whether the levels of antibody to the various foods propose that each one is “safe” to eat, best to eat in moderation, or to avoid entirely.

Other types of testing, such as skin tests, which are dependable for the detection of IgE to environmental allergens, are not dependable for the detection of food allergies.

A further refinement in food allergy testing is the development of the bloodspot test, which requires only a tiny quantity of blood for testing of 45-95 food antigens.

The patient pricks a finger with a lancet and then places drops of blood on a blood spot collection card. The card is air-dried and returned to the laboratory for assessment of IgG4 antibodies to food via ELISA assay. IgG4 results are ranked according to their concentrations in the blood and then ranked according to those results, such as safe, moderately safe, or avoid. These results can then be used to design therapeutic elimination or rotation diets.

IgG Antibodies Detectible Before IgE

IgG antibodies to food are often detectible before IgE antibodies are elevated for common allergic inhalants in children who appear at first to be non-atopic.

In a cross-sectional prospective study of the relationship between IgG in foods and IgE in known allergens, researchers found that, when IgG levels were measured in 120 atopic and 144 non-atopic children, the atopic children had higher IgG levels, particularly for egg white, orange, and milk. These levels correlated with an increased risk of IgE-mediated allergy to cats, dogs, mites, milk and eggs. 14

Sensitization to foods as an increased risk of sensitization to inhalant allergens has been substantiated in a prospective study of 397 IgE-negative children, ages 1-5.

Children who were initially IgE-negative for antibodies to mites, dogs and cats were assessed for IgG antibodies to foods. Two years later, 12.8% of the children showed IgE sensitization to dog, cat or mite antibodies along with increased IgG antibody levels for a combination of wheat-rice or orange. It was concluded that elevated levels of IgG to orange and wheat-rice, along with other factors, increased the risk of IgE-mediated allergies to inhalants. 15

In recent years, clinical studies demonstrating that IgG antibody testing is an effective and dependable testing method own been conducted in children and in patients with migraine, irritable bowel syndrome (IBS), and gluten sensitivity.

Design and Methods

Design overview

Blood draws were performed with the same donor for 3 diverse evaluations: 1) within test repeatability for 2 diverse diagnostic tests on a single sample, 2) within participant repeatability over time, and 3) interlaboratory reliability between diagnostic food allergy testing methods (see Figure 1).

Blood collection

Blood was collected using collection tubes or strips provided by each allergy testing company used in the study.

The companies use diverse methods to determine allergic reactions. Alcat (hereafter referred to as cell size variability method) in Deerfield Beach, FL, uses an assay that measures cell size. US Biotek (hereafter referred to as the IgG ELISA method) in Seattle, WA, uses an assay that measures antibody (IgG) concentration.

For the cell size assay, blood was collected into 2 blue-top vials provided (3.8% sodium citrate, 4.5 ml draw). Blood was shipped overnight at room temperature. Peripheral blood collected for the IgG antibody assay was collected on filter paper strips from a finger stick using a lancet.

Blood was allowed to dry on the filter strips at room temperature and shipped via the US Postal Service.

Cell size testing

Cell size variability is measured to determine reactivity to food antigens. Cells from the blood sample are incubated with potential food allergens. If the individual is sensitive to the food, the cell size changes, most likely due to activation or degranulation. A modified Coulter counter is used to measure cell size.

Antibody testing (ELISA)

Antibody (IgG) specific for a food allergen is measured via ELISA. Food antigens are bound to the surface of an ELISA plate and an individual’s whole blood is added.

If the individual has antibodies to the food, the antibodies will bind to the antigen. These antibodies can then be detected with an enzymatic or colorimetric reaction.

Within test repeatability

The first part of the protocol was designed to assess repeatability within a testing method as a measure of reliability and reproducibility. Blood was collected from the same donor for every time points. On day 1, the several tubes of blood were collected during the same blood draw; the tubes were blinded and sent to both companies for analysis (see Figure 1).

Within participant repeatability over time

Two days after the initial draw (day 2), 2 blood samples were collected during the same blood draw.

The tubes were blinded and sent to both companies for analysis. The next day (day 3), 2 tubes of blood were collected during the same blood draw. The tubes were coded and sent to both companies for analysis. The samples from days 1, 2, and 3 were compared to see if results were consistent over the course of 4 days. A coefficient of variance (CV) and an intraclass correlation coefficient (ICC) were calculated for each test methodology. For the ICC, a worth approaching 1 confirms consistency between the samples. Results were compared between companies in order to determine interlaboratory correlation.

Conclusion

While the mechanism associated with IgG-mediated food allergy may as yet be unknown, the results achieved from serum IgG assessment are extremely clear and provide a valuable means of designing effective treatments.


Total IgG Versus IgG4 Food Allergy

Immunoglobulin G (IgG) is classified into several subclasses termed 1, 2, 3, and 4.

IgGs are composed of two heavy chain–light chain pairs (half-molecules), which are connected via inter–heavy chain disulfide bonds situated in the hinge region (Figure 1). IgG4 antibodies generally represent less than 6% of the entire IgG antibodies. IgG4 antibodies differ functionally from other IgG subclasses in their lack of inflammatory activity, which includes a poor ability to induce complement and immune cell activation because of low affinity for C1q (the q fragment of the first component of complement).

Consequently, IgG4 has become the preferred subclass for immunotherapy, in which IgG4 antibodies to antigens are increased to reduce severe antigen reactions mediated by IgE. If antigens preferentially react with IgG4 antibodies, the antigens cannot react with IgE antibodies that might cause anaphylaxis or other severe reactions. Thus, IgG4 antibodies are often termed blocking antibodies. Another property of blood-derived IgG4 is its inability to cross-link identical antigens, which is referred to as «functional monovalency».

IgG4 antibodies are dynamic molecules that exchange half of the antibody molecule specific for one antigen with a heavy-light chain pair from another molecule specific for a diverse antigen, resulting in bi-specific antibodies that are unable to form large cross-linked antibodies that bind complement and thus cause subsequent inflammation(16). In specific immunotherapy with allergen in allergic rhinitis, for example, increases in allergen-specific IgG4 levels indeed correlate with improved clinical responses.

IgG4 antibodies not only block IgE mediated food allergies but also block the reactions of food antigens with other IgG subclasses, reducing inflammatory reactions caused by the other IgG subclasses of antibodies to food antigens.

In IgG mediated food allergy testing, the goal is to identify foods that are capable of causing inflammation that can trigger a large number of adverse reactions. IgG1, IgG2, and IgG3 every are capable of causing inflammation because these antibodies do not exchange heavy and light chains with other antibodies to form bispecific antibodies.

Thus, IgG1, IgG2, and IgG3 antibodies to food antigens can and do form large immune complexes or lattices that repair complement and increase inflammation. The presence of IgG4 antibodies to food antigens indicates the presence of antibodies to foods that will not generally cause inflammation even though high amounts of these antibodies do indicate the presence of immune reactions against food antigens. Testing only for IgG4 antibodies in foods limits the ability of the clinician to determine those foods that are causing significant clinical reactions that are affecting their patients. The importance of measuring other subtypes of IgG antibodies is highlighted in an article by Kemeny et al.

(17). They found that IgG1 antibodies to gluten were elevated in every 20 patients with celiac disease but none of the patients had elevated IgG4 antibodies to gluten.

Results

Reliability of food allergy testing on a single divide sample.

In this study, blood from 1 person was sent to 2 diverse labs to test for food allergies. On the first day, the blood was divide into 4 samples, and 2 samples were sent to each lab. The 2 samples analyzed by each individual lab were compared for similarity.

This allowed us to test the internal reliability of each lab. The results were reported as no reaction (0), low reaction (1), moderate reaction (2) or high reaction (3). If the food reactivity levels differed between the samples, the difference was calculated and reported in Table 1. The difference between reactivity levels was 0 if a food showed up in the same category in both samples. Cabbage had 1 test reporting a moderate reaction (2), and 1 test reporting a high reaction (3), so the difference in reactivity level was 1 since the results differed by 1 category.

To get a score of 3, 1 sample had a high reaction (3) and 1 sample had no reaction (0).

The company using the cell size variability method tested 50 foods in its food allergy panel. Table 1 demonstrates that only 34% of the foods (17 foods) generated identical results between the divide samples. Twenty-eight percent of the foods (14 foods) differed by 1 reactivity level, 10% of the foods (5 foods) differed by 2 reactivity levels, and 28% of the foods (14 foods) differed by 3 reactivity levels. If this were a dependable test for food allergies, we would expect the majority of the foods tested to own identical results. In this case, 66% of the foods tested differed by 1 or more reactivity levels.

The scatterplot for cell size testing method, Figure 2A, depicts a large variability in the results for the divide sample.

Table 1: This table compares results from a divide sample. The reactivity level differences refer to the percentage of samples that own identical results, or results that are off by a number of categories. For this purpose, no reaction = 0, low = 1, moderate = 2, and high = 3. The reactivity level difference is calculated by taking the absolute difference between the divide sample scores.

The company using the IgG ELISA method tested 96 foods in its food allergy panel.

In contrast to the cell size variability method, 95% of the foods (91 foods) were identical between the divide samples. Five percent of the foods (5 foods) differed by 1 reactivity level. No foods differed by more than one reactivity level between the divide samples. The scatterplot for the IgG ELISA method, figure 2B, has a more linear pattern.

Consistency of food allergy testing over time

On 3 diverse days, samples were collected and sent to both labs to test the consistency of test results over the course of a week. A entire of 4 time points were compared: 2 samples from Monday, 1 sample from Wednesday, and 1 sample from Thursday.

The difference in reactivity levels was recorded as the greatest difference in the 4 time points compared. For example, if lamb had no reaction (0) for 3 time points, and high (3) for 1 time point, it would get a difference in reactivity of 3 (the difference between 0 and 3). If every 4 time points were identical for a food, the difference was scored as 0. If 1 food had a low reaction (1) for 1 time point, moderate reactions (2) for 2 time points and high reaction (3) for 1 time point, the largest difference between reactivity levels was calculated at 2 (the difference between 1 and 3).

As shown in Table 2, 2% of the samples (1 of 50 foods) tested by the cell size variability method yielded identical results over the 4 time points.

Twelve percent (6 foods) differed by 1 reactivity level. Twenty-six percent of foods (13 foods) differed by 2 reactivity levels, and 60% of foods (30 foods) differed by 3 reactivity levels. This means that 60% of the foods had at least 1 sample that scored no reaction at 1 time point and scored high reaction for the same food at a diverse time point during the same week. When comparing every 4 time points, the coefficient of variance for the cell size variability method was calculated to be 0.55, with an ICC of 0.01.

Over the Course of a Week Cell Size Method (# of foods out of 50 tested) IgG ELISA Method (# of foods out of 96 tested)
Identical results 2% (1) 82% (79)
1 reactivity level difference 12% (6)

17% (16)

2 reactivity level difference 26% (13) 1% (1)
3 reactivity level difference 60% (30) 0%
Coefficient of variance (CV) 0.55 0.05
Intraclass correlation coefficient (ICC) 0.01 0.99

Table 2: Results in table 2 show the differences in 4 samples every taken over the course of 4 days.

See Procedure section for more details on the samples taken during 1 week. The reactivity level difference in this table reflects the greatest absolute difference between the 4 samples.

Comparatively, 82% of the foods tested (79 of 96 foods) by the IgG ELISA method produced identical results over the 4 time points. Seventeen percent (16 foods) differed by 1 reactivity level. One percent (1 food) had a reactivity level difference of 2 (one sample, no reaction and three samples, moderate reaction). There were no foods that differed by 3 reactivity levels over the 4 time points. The coefficient of variance was 0.05 for the IgG ELISA method, with an ICC of 0.99, which demonstrates a much more consistent reactivity pattern.

Celiac Disease and Non-celiac Gluten Sensitivity

No discussion of allergy testing would be finish without addressing gluten sensitivity and gluten intolerance.

Celiac disease, also known as gluten-sensitive enteropathy, is a food intolerance that affects individuals with a genetic predisposition to react to gliadin, a gluten protein found in wheat, barley, and rye. While the exact mechanism is unknown, exposure to these proteins causes an inflammatory reaction and increased intestinal permeability 30, 31 leading to symptoms of diarrhea, malabsorption, and irritable bowel syndrome. Chronic exposure leads to atrophy of the villi of the little intestine. 32 To date, the only effective treatment for celiac disease is a gluten-free diet.

Definitive diagnosis of celiac disease is confirmed through biopsy of the little intestine, with serological testing for anti-gliadin (AGA), IgA and IgG, anti-endomysial (EMA), and anti-tissue transglutaminase (tTG) antibodies conducted as part of the diagnostic evaluation.

Serum IgG antibody testing for gluten/gliadin antibodies is done using an FDA-approved ELISA.

Research has shown that gluten sensitivity may, in fact, happen without villous atrophy being apparent. 33, 34 Other tissues may be targeted in gluten-sensitive individuals, manifesting as autoimmune diseases or skin conditions, such as dermatitis herpetiformis. Some own recommended that early diagnosis, using serum anti-gliadin IgG testing before tTG or EMA levels are elevated and before villous atrophy has occurred, can assist identify those who are at risk and prevent progression of the disease through gluten avoidance. 35

There is a large group of people in our population, however, who react to gluten and are “gluten sensitive” and do not own celiac disease.

Clinical evidence suggests that a gluten-free diet in these individuals, based upon serum IgG levels, reduces symptoms and improves health in a vast majority of those assessed. Preliminary studies are now underway to identify the mechanism with which gluten affects the body in those who are gluten sensitive but without identifiable celiac disease. 36

Discussion

An ideal response to food antigen is tolerance. Yet, some patients develop allergic responses to seemingly innocuous food antigens. Clinicians commonly recommend lab testing when a patient has a suspected food allergy. It is possible that some types of food reactivity will show up in 1 type of testing method and not others.

Clinicians and patients rely on the lab tests to be both precise and reproducible. When a physician reported that 2 types of food allergy tests reported diverse results for a single patient, we tested the reliability of food allergy testing for the 2 types of food allergy tests in question. Although both of these labs are Clinical Laboratory Improvement Amendments (CLIA)– certified, certification does not ensure the consistency and reproducibility of laboratory tests.

Before we could examine interlaboratory results of food allergy testing, intralaboratory reliability needed to be evaluated.

Excellent intralaboratory reproducibility means that when a sample is compared with itself (as in a divide sample), the results are expected to be identical. Similarly, when a person maintains a normal dietary routine over the course of a week, the results of a food allergy test would be expected to be the same. In this study, the cell size variability method delivered extremely diverse results for every the samples submitted, and therefore had no internal reproducibility or accuracy. The IgG ELISA method had excellent intralaboratory correlation for the divide sample and the samples analyzed over the course of a week.

The unreliability of the cell size variability method results prevented an interlaboratory analysis comparing the results of the cell size variability method to the IgG ELISA method.

Other researchers own compared allergy testing methods, although most studies focus on IgE-related allergies as opposed to IgG-mediated responses. Double-blind placebo-controlled food challenge (DBPCFC) is considered the gold standard in food allergy testing and is strongly correlated with IgE testing.26,27 In this type of testing, the reaction of a suspected allergenic food is compared to a placebo food, known to not evoke a response.

Foods that are known to induce anaphylaxis are not generally tested. The DBPCFC identifies foods that evoke immediate food allergy symptoms.28 Skin tests can also be used to identify food allergens. These tests are more sensitive than IgE blood tests.29

IgE to food allergens demonstrates an immediate phase immune response. Delayed type responses, however, are not mediated by IgE antibodies and will not show up with this type of testing.30 For symptoms of food allergies caused by delayed type hypersensitivity reactions such as headaches, mood swings, intestinal upset, pain, and attention problems, the DBPCFC or skin tests may present a untrue negative.

In this study, IgG ELISA testing was more reproducible than cell-size testing.

In general ELISA is known to be consistent and is routinely used for scientific testing.31 The sensitivity of ELISA as a method for food allergy testing is dependent upon the food antigen used as well as the quantity of antibody present. IgE food antigens used for ELISA assays own been standardized and are consistent between diverse laboratories. IgG food antigens own not been standardized, which accounts for some of the variation between laboratories.

Every commercial food antigens for ELISA testing are made from raw foods (both IgE and IgG antigens). Cooking food exposes diverse antigens and epitopes which may affect ELISA test results.32 For example, pecans, wheat flour, roasted peanuts, lentils, almonds, cashews, walnuts, soy beans, shrimp, scallop, tuna, egg, apple, plum, milk, and potatoes own been shown to own antigens that differ between raw and cooked forms.33,34 Another researcher suggests that cooked egg (baked egg especially) produces less of a reaction than raw egg.35

The participant of this study had IgG reactions to milk and soy.

The most common IgE mediated food allergens in the general population are milk, soy, egg, peanut, wheat, tree nuts (walnuts and cashews), fish, and shellfish. These foods account for 85% of the commonly recognized food allergens.36 The other foods with high reactions for this participant included almonds, corn, lima beans, bananas, and blueberries. Every of these foods were regularly included in the participant’s diet before the food allergy tests.

Cell size testing as a measure of food reactivity is not well studied in the literature.

Consistent with the data reported herein, most studies propose that it is unreliable.37,38,39 The company that performed the cell size variability method was told of the results in a phone call a month after the testing was finish and said that there were no irregularities during that week and that they stood by their results. While we can hypothesize a mechanism for identifying food allergies from cell size differentials, the data clearly protest this method is not specific, not reproducible, and was not related to food reactions in this participant. As the scientific community continues to understand the importance of the antigen being used and the accuracy of diverse tests in providing relevant clinical guidance, the consistency between laboratories and the method they employ must improve.

Irritable Bowel Syndrome (IBS)

Irritable bowel syndrome (IBS) is a complicated disorder in which patients experience abdominal pain and discomfort with frequent bouts of diarrhea or constipation.

Treatment is challenging and numerous traditional methods used to predict it are disappointing, with diagnosis based on exclusion in most cases. 20 While IBS may own numerous causes, patients remain convinced that dietary intolerance and food sensitivities are at the root of the problem. When certain foods are eliminated from the diet of IBS patients, they improve, making dietary modification through elimination of specific foods and food challenge an effective strategy.

In a extremely clear, double-blind, randomized, controlled study, 131 participants between the ages of 18 and 75 with uncomplicated IBS were enrolled with two outcome measures.

The first was to assess what would happen to symptom severity when participants were put on elimination diets based upon their IgG antibodies to foods. The second objective of the study was to measure changes in symptom severity when foods were reintroduced in the diet. 21

IgG antibodies were measured using an enzyme-linked immunosorbant assay (ELISA) test designed to measure antigens to 29 diverse foods.

Patients were assigned to groups to get either a “true” or a “sham” elimination diet based upon detected IgG antibody levels. Symptom severity was assessed for each patient prior to the study, along with atopic status. On average, most study participants had had symptoms of IBS for 10 years and, on average, had elevated IgG titers to 6-7 foods.

At the finish of the 12-week study, symptom severity decreased by 10% in those on the true diet. While improvement was greatest among participants on the true diet, there was some improvement noted in symptom severity for those on the sham diet, suggesting there was some little placebo effect.

In participants who were fully compliant with the true diet and had the highest level of sensitivity to foods as demonstrated by their IgG titers, there was a 26% improvement in symptom severity.

This was not true for participants with high sensitivity who were on the sham diet, however.

When foods with high IgG antibody titers were reintroduced to the diet, symptom severity increased in those on the true diet by 83% and by 31% in the sham group. 22

In another study involving 25 participants with irritable bowel syndrome (IBS), dietary modification was sure following measurement of their IgG4 antibody levels to specific foods. IgG4 antibody levels were assessed for beef, pork, lamb, chicken, fish, shrimp, yeast, tomatoes, peanuts, milk, eggs, cheese, wheat, rice, potatoes, and soybeans and foods with titers over 250 mcg/l were eliminated from the diet for 6 months.

The highest titers were recorded for beef, pork, lamb, eggs, milk, and wheat. When assessed at 6 months, study participants reported reduced pain and pain frequency, reduced bloating, improvement in bowel habits, and improvement in quality of life. 23

More recently, a study comparing IgG, IgE and entire IgE antibody titers was conducted in patients with IBS and functional dyspepsia (FD). Serum IgG and IgE antibody titers were measured for 14 foods, including tomatoes, wheat, crab, codfish, eggs, corn, mushrooms, milk, port, rice, shrimp, beef, chicken and soybeans.

As in similar studies, there were no significant levels of food-specific IgE antigens. However, IgG levels were elevated for crab, egg, shrimp, soybean, and wheat as compared to controls in patients with IBS. In patients with FD, IgG antibodies were significantly higher for egg and soybean. While there were elevations in IgG food-specific antigens, there was no correlation to symptom severity. 24

In yet another study, 108 study participants with IBS were tested for their sensitivity to 16 foods using IgG4 and IgE titers and skin prick testing.

Study participants had the highest IgG4 titers to wheat, beef, and lamb, with no significant results reported for potatoes, rice, fish, chicken, yeast, tomato, or shrimp. In contrast, IgE titers were not elevated in study participants or controls and skin prick testing showed only one positive result in 5 of 56 patients. Researchers concluded that there is a possible pathophysiological basis for the IgG4 antibodies detected in patients with IBS. 25 While the mechanism may not yet be clarified, mucosal inflammation and immunological reactivity appear to be a factor in IBS and deserve further study.

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Treatment with elimination and rotation diets has also been shown to be effective for IBS patients who are not responsive to other forms of therapy. In an open label pilot study, 25 patients with diarrhea dominant IBS 27 were first screened for their serum IgG4 and IgE titers, along with mold antigen panels. Every patients had baseline antibody abnormalities and were given elimination diets based upon their antibody levels and asked to follow them for up to 4 weeks.

After the elimination phase, foods were challenged and reintroduced in a rotation diet if there were no symptoms. Any food causing symptoms was eliminated from the diet for an additional 6 months. Study participants were given probiotics for 4 months out of the 6-month trial period.

At the finish of the trial period, patients reported improvement in stool frequency and quality of life scores. Most patients sustained their clinical improvement one year after the trial ended, reporting few symptoms and continued adherence to the rotation diet. 28

Eliminating foods based upon IgG4 levels in patients with IBS has been sure by other researchers to be a extremely valuable treatment modality.

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Acknowledgements

Helfgott Research Institute provided funding for this study and consulted on the study design. William Gregory, PhD, provided statistical consultation and comments on the manuscript.

Between Divide Samples Cell Size Method (# of foods out of 50 tested) IgG ELISA Method (# of foods out of 96 tested)
Identical results 34% (17) 95% (91)
1 reactivity level difference 28% (14) 5% (5)
2 reactivity level difference 10% (5) 0%
3 reactivity level difference 28% (14) 0%


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