Without a doubt, food is an important aspect of our physical and mental health. The food we eat has a significant impact on our health and the development of diseases. Food products can not only contribute to normal life and the easier course of diseases, but also cause chronic inflammatory processes in our body, cause chronic diseases (the most famous of them is celiac disease) and even lead to anaphylactic shock. Anaphylactic shock is an abnormal reaction of the immune system to a harmless protein, the main role of which is played by IgE. Today, the chronic inflammatory process that can be caused by food is not studied enough. Determination of food-specific IgG may be the best marker for identifying foods that cause chronic inflammation. It is elimination diets, based on the results of IgG studies, that significantly improve the course of a number of chronic diseases.

Is there new evidence for the role of IgG-mediated immune response in the development of food intolerance?

New scientific publications indicate that IgG may also be involved in anaphylaxis. However, it appears that larger amounts of antigens and antibodies are required than in the case of IgE. The assumption made in all past publications, which is also the basis of allergists’ arguments that IgG represents a “normal” reaction without clinical impact, should be rejected even in type 1 allergy. Some authors showed that IgG and IgA isotypes were significantly detected in three allergic conditions, even in the absence of IgE. All allergic patients, including those with only IgG and IgA antibodies, showed significant improvement in symptoms and significantly reduced levels of beef-specific antibodies in response to a cow-free diet. Specific IgG and IgA antibodies coexist with IgE antibodies in the blood serum of allergic patients and are significantly related to the clinical course of allergic disorders, particularly asthma. It is likely that IgG-mediated reactions predominately cause milder reactions in humans. Also, these reactions can occur with a delay in time. As you know, food is absorbed from the intestinal mucosa. This will dilute the antigen, and the response will become dose-dependent, a phenomenon observed when consuming foods to which a person has IgG antibodies.

Contradiction between IgG and IgG4

Several authors have described the difference between IgE-mediated food allergy and delayed-type IgG-mediated food allergy. IgG is divided into 4 subclasses, IgG1, IgG2, IgG3 and IgG4. IgG4 is associated with type 1 allergy and can be considered as an antidote to IgE. IgG4 does not opsonize the antigen and does not activate complement. IgG4 is a clearing antibody that does not cause inflammation. IgG1, IgG2, and IgG3 all have opsonizing properties and are able to activate the complement required for an inflammatory response. IgG4 is not recommended for the detection of adverse food reactions, as stated in the EAACI position paper. IgG4 is present in the blood in much lower concentrations than other subclasses. The sensitivity of IgG4 food sensitivity tests is designed to detect only very high levels of IgG4. This is important because low IgG4 values ​​are unimportant, but higher IgG4 values ​​can generate histamine, which can lead to pseudoallergic symptoms in patients with low DAO activity. Therefore, it is advisable to avoid these products as well.

Arguments put forward by allergy societies

The claims and comments made in multiple posts are misleading as they all relate to type 1 allergies. No one in the field of IgG testing is referring to type 1 allergy. The following statements are true about type 1 allergies, but not about delayed-type allergies.

Not all IgG-positive products cause specific symptoms

The main criticism raised in all the papers challenging the significance of IgG is that not every positive IgG response leads to a symptom. Therefore, these reactions are often classified as “non-specific” or “false positive”. By the way, these statements are also true for the gold standard for type 1 allergy, IgE. Not every positive IgE is automatically associated with a symptomatic allergic reaction. Assuming that the testing system used has no technical reason for such false positives and that the presence of detectable IgG is real, this result should receive the same attention as any food that causes a particular symptom. We could see that each IgG-positive product was responsible for water retention, a sign of an inflammatory response. Another objection is that IgG-driven elimination diets lead to the elimination of too many foods, causing malnutrition and micronutrient deficiencies. Thus, there are special recommendations for introducing foods to which IgG antibodies have been detected:

1. Rotational Diet: Each person should change foods every 4-5 days, that is, eat the same food only every 5th day. Which automatically means that he or she should eat different foods every day, avoiding a monotonous diet and malnutrition. An average Western diet is by definition more monotonous than a rotational diet.
2. After a 3-month diet, when the immune system has stabilized and inflammation has subsided, we begin re-introducing foods one at a time (challenge test) to identify foods that cause specific symptoms. This principle is also used in IgE-mediated allergy and is the final confirmation of clinically significant allergy.

It is obvious that after passing the intestinal barrier, the reaction between antigen and antibody (IgG) will lead to the formation of an immune complex and that this immune complex will be destroyed by immune cells. In most cases, this will be circulatory and will not cause any specific symptoms other than water retention. Some authors have shown the pro-inflammatory effect of a mixed meal. In some people, this will lead to a decrease in insulin sensitivity, which in the long term can lead to insulin resistance and related weight problems. The impact of low-grade chronic inflammation on insulin resistance and obesity is widely substantiated today by many authors.

In practice, it was possible to notice that in the case of weight problems, every positive product was important. In the case of a particular symptom, in most situations only 1 or 2 products were responsible for the symptom. It was also observed that certain foods that were positive and did not cause symptoms at the time of testing became significant after some time, causing a new symptom.

If the products are eaten regularly, chronic inflammation will sooner or later occur at the local level and lead to a specific symptom. This also explains why not every product causes a particular symptom or the same symptom. It solely depends on individual inclination. But it also explains the common indicators that are positively affected by IgG-mediated elimination of products. It depends on the patient’s genetics, previous injuries or infections. It also shows that food is not the primary cause, but a constant trigger for inflammation and co-morbidities in the presence of an IgG-mediated response. Therefore, identifying and avoiding such products is extremely important for possible treatment.

Inappropriate interpretation of publications

The articles cited by the Society of Allergists to show the insignificance of IgG refer exclusively to type 1 allergies. A very small number of publications rely on scientific papers on the IgG-mediated immune response. No published scientific article supports the allergist societies’ claims. All statements are disputed and represent the personal opinion of individuals without reliance on scientific works. The old judgments of some medical societies, which have been refuted in recent years and which apply only to type 1 allergies, are being repeated. The scientific discussion should also take into account all the published articles in favor of IgG, which have increased in recent years. There is increasing evidence for a role for dietary IgG in PCOS, inflammation and hypertension, migraine, respiratory disease, Crohn’s disease (37), behavioral problems such as schizophrenia, and asthma.

Why do we recommend choosing the FOX test?

• Nano-technology
• 286 food antigens from 13 food groups
• Main products used in our country and in the world
• Blood serum is used for the analysis
• FOX is used by:

– to clarify dietary status

– to monitor compliance with the diet

– with immunologically caused food intolerance

– for diagnosis of sensitivity to food products

– with “leaky” bowel syndrome

Usually, the main reason for the current controversy is that the allergy societies confuse the specific total IgG test with the IgG4 test, which is considered inappropriate in allergic diseases. In most publications on allergy studies, IgG4 was used as a marker. As described above, the main indications for testing for total specific IgG are not classical allergic diseases, but chronic inflammatory diseases in which no recommended medical treatment is successful. It is also critical to note that allergy society publications do not treat this topic from a scientific perspective, citing pro and con articles, but only anti publications, which in most cases are not even scientific papers. Another issue is that previously the reliability of some proposed IgG tests was not stable. Certainly, more research is needed for full acceptance in the medical community.

Sources:

1. Mouse and human neutrophils induce anaphylaxis. Jönsson F, Mancardi DA, Kita Y, Karasuyama H, Iannascoli B, Van Rooijen N, Shimizu T, Daëron M, Bruhns P. J Clin Invest. (2011) Apr 1; 121(4): 1484-96
2. Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglob- ulin-E-mediated systemic anaphylaxis. Tsujimura Y, et al. Immunity. (2008);28(4):581–589
3. Pathways of anaphylaxis in the mouse. Strait RT, Morris SC, Yang M, Qu XW, Finkelman FD. J Allergy Clin Immunol. (2002);109(4):658–668.
4. IgG-mediated systemic anaphylaxis to protein antigen can be induced even under conditions of limited amounts of antibody and antigen. Ishikawa R, Tsujimura Y, Obata K, Kawano Y, Minegishi Y, Karasuyama H. Biochem Biophys Res Commun. (2010) Nov 26;402(4):742-6.
5. Anaphylaxis: lessons from mouse models. Finkelman FD. Department of Medicine, Cincinnati Veterans Affairs Medical Center, Ohio, USA. J Allergy Clin Immunol. (2007) Sep; 120(3): 506-15
6. Testing for Food Reactions : The Good, the Bad, and the Ugly Gerard E. Mullin, Kathie M. Swift, Liz Lipski, Laura K. Turnbull and S. Devi Rampertab. Nutr Clin Pract (2010) 25: 192
7. Immunologie, textbook Charles Janeway, Paul Travers, Mark Walport, Mark Shlomchick, Spektrum akademischer Verlag 5th edidtion (2002) 388-389 ISBN 3-8274-1079-7
8. Inhibition of complement activation by IgG4 antibodies. Van der Zee JS, van Swieten P, Aalberse RC. Clin. Exp. Immunol. (1986) May: 64 (2):415-22
9. Immunoglobulin G4: an odd antibody. Aalberse RC, Stapel SO, Schuurman J, Rispens T. Clin Exp Allergy, (2009) 39 (4):469-77.
10. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Steven O. Stapel , R. Asero , B. K. Ballmer-Weber 3 , E. F. Knol , S. Strobel, S. Vieths , J. Kleine-Tebbe Allergy (2008) 63:793–796
11. Nahrungsmittelunverträglichkeit (Histamin Intoleranz) [Taschenbuch] Grace M. D. Abbot; Camille Lieners; Isabella Mayer; Albert Missbichler; Markus Pfisterer; Helmut Schmutz (2006) ISBN: 3950228705
12. Keine Empfehlung für IgG und IgG4-Bestimmungen gegen Nahrungsmittel. Leitlinie der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI), des Ärzteverbandes Deutscher Allergologen (ÄDA), der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI) und der Schweizerischen Gesellschaft für Allergologie und Immunologie (SGAI) nach Übernahme des Task Force Report der European Academy of llergology and Clinical Immunology (EAACI). Kleine-TebbeJ,ReeseI,Ballmer-WeberBKetal Allergo J (2009)18:267– 273
13. Unproven diagnostic procedures in IgE-mediated allergic diseases. Niggemann B, Gruber C Allergy (2004) 59:806–808
14. In-vitro Allergiediagnostik. Leitlinie der Deutschen Gesellschaft für Allergologie und Klinische Immunologie (DGAKI) unter Beteiligung des Ärzteverbandes Deutscher Allergologen (ÄDA), der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA) und der Deutschen Dermatologische Gesellschaft (DDG). Renz H, Biedermann T, Bufe A et al Allergo J (2010)19:110–128
15. Allergenfamilien und molekulare Diagnostik IgE-vermittelter Nahrungsmittelallergien: von der Theorie zur Praxis. Kleine-TebbeJ, MeißnerAM, JappeU, HeroldDA Allergo J (2010)19:251–263
16. Meat-specific IgG and IgA antibodies coexist with IgE antibodies in sera from allergic patients: clinical association and modulation by exclusion diet. Calderon TE, Ferrero M, Marino GM, Beltramo D, Rabinovich GA, Romero MD. J.Biol.Regul.Homeost.Agents (2010) Jul-Sept: 24 (3): 261-71
17. In-vitro-Diagnostik und molekulare Grundlagen von IgE-vermittelten Nahrungsmittelallergien. Leitlinie der Deutschen Gesellschaft für Allergie und Klinische Immunologie (DGAKI), des Ärzteverbandes Deutscher Allergologen (ÄDA) und der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI) und der Schweizerischen Gesellschaft für Allergologie und Immunologie (SGAI). Kleine-TebbeJ, Ballmer WeberB,BeyerKetal Allergo J (2009)132–146
18. Bioresonanz – diagnostischer und therapeutischer Unsinn. Stellungnahme der Fachkommisssion der Schweizerischen Gesellschaft für Allergologie und Immunologie (SGAI) zu den Bioresonanz- und Elektroakupunkturgeräten zur Diagnostik und Therapie von (vermeintlichen) Allergien. WüthrichB, FreiPC, BircherAJetal. Akt Dermatol (2006)32:73–77
19. Sinnlose Allergietests. Eine Stellungnahme der Fachkommission der Schweizerischen Gesellschaft für Allergologie und Immunologie (SGAI) zur IgG/IgG4-Bestimmungen gegen Nahrungsmittel. WüthrichB,FreiPC,BircherAJetal Allergologie (2005) 465–468
20. Sinnlose diagnostischeTestsund Therapieverfahren in der Allergologie – ein zunehmendes Problem. Wüthrich B Dermatology (2010) 16:103–118
21. AllergenspezifischeT-Zell-Antwortbei Ekzemkrankheiten (Habilitationsschrift). Werfel T. (2000) Fortschritte der Allergologie und Immunologie. Dustri, Deisenhofen München
22. Increase in intra- nuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. Aljada A, Mohanty P, Ghanim H, et al. Am J Clin Nutr (2004); 79:682–690.
23. Increase adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM.. J Clin Invest (1995); 95: 2409-2415.
24. Adipose expression of tumor necrosis factor- direct role in obesity-linked insulin resistance. ) Hotamisligil GS, Shargill NS, Spiegelman BM. .Science (1993); 259: 87-91.
25. Inflammation and metabolic disorders Hotamisligil GS,Nature, (2006), 444, 860-867 (26) Ungeeignete Testverfahren in der Allergologie J. Kleine-Tebbe. D. A. Herold Hautarzt (2010) 61: 961-966
26. Food allergy in irritable bowel syndrome: new facts and old fallacies. Isolauri E, Rautava S, Kalliomaki M, (2004) Gut; 53 (10):1391-3
27. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Atkinson W, Sheldon TA, Shaath N and Whorwell PJ. (2004) Gut 53(10):1459-1464.
28. Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics. Drisko J, Bischoff B, Hall M and McCullum (2006). J of the Am college of Nutrition. Vol25 (6) 514-522
29. Alterations of food antigen-specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia X. L. Zuo, Y. Q. L, W. J. Li, Y. T. Guo, X. F. Lu, J. M. Li and P. V. Desmond Clinical and Experimental Allergy, (2007) 37, 823–830
30. Dietary Treatment of the Irritable Bowel Syndrome Peter Whorwell, MBChB, MRCP and Richard Lea, BSc, MD, FRCP Current Treatment Options in Gastroenterology (2004), 7:307-316
31. IgG antibodies against food antigens are correlated with inflammation and intima media thickness in obese juveniles. Wilders-Truschnig M, Mangge H, Lieners C, Gruber HJ, Mayer C and Marz W. (2007). Exp Clin Endocrinol Diabetes
32. A prospective Audit of food intolerance among migraine patients in primary care clinical practice. Trevor Rees, David Watson, Susan Lipscombe, Helen Speight, Peter Cousins, Geoffrey Hardman, Andrew Dowson. (2005) Headache, Vol 2 No.1 11-14
33. (34) Food allergy mediated by IgG antibodies associated with migraine in adults. Arroyave Hernandez CM, Echevarria Pinto M, Hernandez Montiel HL. Rev Alerg Mex (2007); 54: 162–168
34. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C and Baykan B. (2010) Cephalgia 1-9.
35. Treatment of delayed food allergy based on specific immunoglobulin G RAST testing. Dixon H. (2000). Otolaryngology- Head Neck Surgery Vol 123:48-54
36. Clinical relevance of IgG antibodies against food antigen in Crohn’s Disease – A double blind cross over diet intervention study S. Bentz, M. Hausmann, S. Paul, W. Falk, F. Obermeier, J. Schölmerich, G. Rogler Digestion (2010);81:252–264
37. Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Severence EG, Dickerson FB, Halling M, Krivogorsky B, Haile L, Yang S, Stallings CR, Origini AE, Bossis I, Xiao J, Dupont D, Haasnoot W, Yolken RH. Schizophr.Res.(2010) May 118(1-3):240-7
38. Association between bovine casein antibody and new onset schizophrenia among US military personnel. Niehbur DW, Li Y, Cowan DN, Weber NS, Fisher JA, Ford GM, Yolken R. (2011) Schizophr.Res. Mar2. (Epub ahead of print)
39. Ovalbumin-specific immunoglobulin G and subclass responses through the first 5 years of life in relation to duration of egg sensitization and the development of asthma. Vance, G.H.S., Thornton, C.A., Bryant, T.N., Warner, J.A. and Warner, J.O. Clinical and Experimental Allergy,(2004) 34, (10), 1542-1549.
40. Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial. Pelsser LM, Frankena K, Toorman J, et al. Lancet (2011); 377: 494- 503
41. Lebensmittelunverträglichkeit, Allergie Typ 3 erkennen und richtig behandeln. Hans J. Schwyn, Camille Lieners AT-Verlag, (2009) ISBN-10: 3038004154
42. L’Immuno-nutrition, se nourir selon son immunité Dominique Rueff Edition Xavier de Guibert (2007) ISBN 978-2-7554-0107-3
43. Milk protein IgG and igA : the association with milk-induced gastrointestinal symptoms in adults. Anthoni S, Savilahti E, Rautelin H, Kolho KL World J. (2009) Gastroenterol. Oct 21 ; 15 (39) 4915-8
44. The effect of exclusion of dietary egg and milk in the managment of asthmatic children : a pilot study. Yussof NA, Hampton SM, Dickerson JW, Morgan JB, (2004) J.R.Soc Health 124(2) 74-80