Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report*

Abstract

KEYWORDS food allergy • food intolerance • IgG • IgG4 • in vitro tests ABSTRACTSerological tests for immunoglobulin G4 (IgG4) against foods are persistently promoted for the diagnosis of food-induced hypersensitivity. Since many patients believe that their symptoms are related to food ingestion without diagnostic confirmation of a causal relationship, tests for food-specific IgG4 represent a growing market. Testing for blood IgG4 against different foods is performed with large-scale screening for hundreds of food items by enzyme-linked immunosorbent assay-type and radioallergosorbent-type assays in young children, adolescents and adults. However, many serum samples show positive IgG4 results without corresponding clinical symptoms. These findings, combined with the lack of convincing evidence for histamine-releasing properties of IgG4 in humans, and lack of any controlled studies on the diagnostic value of IgG4 testing in food allergy, do not provide any basis for the hypothesis that food-specific IgG4 should be attributed with an effector role in food hypersensitivity. In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity, but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints. ARTICLE TEXTAn adverse food reaction is a general term describing clinically abnormal responses to an ingested food that might occur secondary to nonallergic food hypersensitivity (food intolerance) or allergic food hypersensitivity (food allergy).Food allergy is an immunologic reaction that involves in particular the immunoglobulin E (IgE) mechanism, of which anaphylaxis is the classic example.Food intolerance, however, is a general term, describing an abnormal physiologic response to an ingested food or food additive. Diagnosis of food allergy aims to establish a reliable link between the clinical history of an adverse reaction to food as reported by the patient and the immunological basis of this reaction. In food allergy, an accurate diagnosis is extremely important, in particular to prevent patients from unnecessary and even potentially health threatening diets.Measurement of food-specific IgE antibodies by in vitro assays or skin testing are the routine procedures to diagnose food allergy. These diagnostic tests, however, indicate the presence of food-specific IgE antibodies, but they do not establish the diagnosis of food allergy. The final proof of the clinical relevance of the reported

IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population

“…Therefore, they may consume smaller amounts of dairy products. Food-specific IgG values may reflect exposure to a specific food [5]. In support of our results, decreased IgE levels were associated with elevated levels of IgG antibodies against milk in individuals who had developed a tolerance to cow’s milk after experiencing an allergy to the same product [17], and subjects drinking milk had higher levels of milk IgG in their sera than did non-milk drinkers in one study [18].…”

“…IgE-mediated food allergy is uncommon and explains the symptoms in only a minority of subjects with IBS [3]. IgG antibodies are purposed to give a more delayed response to specific antigens than IgE antibodies [4], and the subclass IgG4 might induce histamine release, like IgE antibodies, and is found to be synthesized under influence of T-helper 2 cytokines like IgE antibodies [5]. One study found higher titres for some food-specific IgG antibodies in subjects with IBS compared to controls, but no significant correlation between symptom severity and IgG antibody titres [6].…”

Misdiagnosed Food Allergy Resulting in Severe Malnutrition in an Infant

“…Of note, the European Academy of Allergy and Clinical Immunology Task Force report and the National Institute of Allergy and Infectious Diseases-sponsored expert panel both recommend against the use of IgG testing for routine evaluation of food allergies, as positive IgG levels likely represent a physiologic response of the immune system after exposure to a food and are not indicative of clinical disease. 6,7 When negative, specific IgE testing yields a high negative predictive value; however, positive specific IgE testing in the serum and skin testing may not be clinically meaningful, as a positive test indicates only sensitization and not necessarily clinical reactivity. Additionally, predictive capabilities of serum testing depend on the testing modality used, as predictive values for clinical reactivity to certain foods have been established using the ImmunoCAP method at this time.…”

Concerning Diet Duration at Cow’s Milk Protein Allergy. How and When Should Dairy Products Be Introduced Again?

“…Специфический IgG4-ответ на пищевые белки в насто-ящее время рассматривается как физиологический [25], при этом показано, что он более выражен при раннем введении молочного белка [26,27]. В дальнейшем спец-ифические IgG4, по всей видимости, вовлечены в форми-рование толерантности к пищевым белкам [28].…”