Testing for IgG 4 against foods is not recommended as a diagnostic tool : EAACI Task Force Report *

An 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 history and the detected food-specific IgE is merely provided by a positive controlled food challenge (1). When IgE-mediated food allergy cannot be established by regular diagnostic procedures, it is not uncommon that disappointed patients, who blame food components for their problems, seek further for confirmation of their personal suspicions elsewhere, looking for test results that are more in line with their expectations. Commercial laboratories all over Europe are currently offering broad-scale IgG4 testing against foods to the public, claiming that these tests represent reliable tools for the diagnosis of food allergies. This idea is probably Serological 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 enzymelinked 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. Steven O. Stapel, R. Asero, B. K. Ballmer-Weber, E. F. Knol, S. Strobel, S. Vieths, J. KleineTebbe Sanquin Diagnostic Services, Amsterdam, the Netherlands; Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italy; Allergy Unit, Department of Dermatology, University Hospital Z! rich, Z! rich, Switzerland; Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, the Netherlands; Peninsula College of Medicine and Dentistry, Institute of Clinical and Biological Sciences, Plymouth, UK; Paul-Ehrlich-Institut, Division of Allergology, Langen, Germany; Allergy and Asthma Center Westend, Berlin, Germany