What is the clinical utility of food-specific IgG testing?

Food intolerance and allergies are generally estimated to affect around twenty percent of the population, with allergies not exceeding ten percent (1). IgE-mediated allergy ranges in presentation from urticaria to anaphylaxis typically within 2 hours of consumption, and non-IgE mediated allergies, whose testing is beyond the scope of this article, present as subacute to chronic conditions isolated to the gastrointestinal tract. Food intolerances are more difficult to define, especially in comparison to non-IgE-mediated food allergy, but they are not considered to be immunologic in nature and often arise from enzymatic or other deficiencies in the digestive tract, with consistent and similar symptoms with each exposure.

Diagnosis of food allergy is usually achieved through a combination of clinical history (essential) and allergen testing. When an IgE-mediated allergy is suspected, the presence of specific IgE may be tested by skin prick and/or serum testing. In skin prick testing, a small amount of allergen is injected subdermally, and the site of injection is monitored for reaction. Reactions are classified by the diameter of the resulting wheal, with larger wheal indicating greater severity of reaction (and in epidemiologic studies providing greater positive predictive value)(1). As an alternative or an adjunct test, allergen-specific IgE may be assayed from serum. The mere presence of a specific IgE to a food may not be clinically significant, and therefore in both skin prick and serum testing, sensitivity is relatively good, while specificity is relatively poor. Therefore, shotgun-style allergy testing (the use of large, unfocused panels) is inappropriate. Instead, selected allergens should be tested based on the patient’s clinical history with respect to exposure(1). After all, if the patient does not eat it, why test for antibodies to it?

Direct-to-consumer food-specific IgG panels have been advertised to consumers as a method for detecting food intolerance. These panels may contain 200 targets or more. Notably, reputable nationwide reference laboratories with names familiar to most laboratorians do not offer such testing. Likewise, the direct-to-consumer sites offering these tests typically include disclaimers with respect to insurance coverage. But what is the significance of food-specific IgG?

Food-specific IgG is currently understood to represent a normal immunological response to food consumed in the diet and a reflection of foods one consumes (2). Food intolerances have not been linked to immunoglobulin-mediated processes, and in fact, food-specific IgG may be linked to tolerance (2). Food-specific IgG has not been demonstrated to have value in the diagnosis of food allergy or intolerance, as reflected in myriad society practice guidelines:

• “IgG measurements cannot be correlated with any clinical symptoms or disease.” European Academy of Allergy and Clinical Immunology (EAACI) (3)
• “Unproved tests, including allergen-specific IgG measurement […] should not be used for the evaluation of food allergy. […] Measurement of food-specific IgG and IgG4 antibodies in serum are not recommended for the diagnosis of non–IgE-mediated food-related allergic disorders.” American Academy of Allergy, Asthma, and Immunology (AAAAI) and American College of Allergy, Asthma, and Immunology (ACAAI)(1)
• There is no body of research that supports the use of [food-specific IgG] to diagnose adverse reactions to food or to predict future adverse reactions.” Canadian Society of Allergy and Clinical Immunology (CSACI)(4)

Because of its reflection of the diet, food-specific IgG panel testing is likely to produce several “positives” leading to over-restriction of the diet (5). Paradoxically, patients with food intolerances acting on the results of these panels may see improvements because the large number of foods they must eliminate may remove the culprit from their diet by coincidence. However, over-restriction can have impacts beyond mere inconvenience, as it may place a patient at risk of nutritional deficiencies and can “detrimentally affect the social aspects of their quality of life” (5).

Laboratories receiving inquiries concerning food-specific IgG testing should educate providers regarding the dubious utility of this testing and direct providers to relevant clinical practice guidelines such as those of the EAACI, CSACI, or the joint guidelines of the AAAAI and ACAAI.

REFERENCES;

1. Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, et al. Food allergy: A practice parameter update—2014. J Allergy Clin Immunol. 2014;134:1016-1025.e43.
2. Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, et al. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Allergy. 2008;63:793–6.
3. Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy. Allergy. 2014;69:1008–25.
4. Carr S, Chan E, Lavine E, Moote W. CSACI Position statement on the testing of food-specific IgG. Allergy Asthma Clin Immunol Off J Can Soc Allergy Clin Immunol. 2012;8:12.
5. Lomer MCE. Review article: the aetiology, diagnosis, mechanisms and clinical evidence for food intolerance. Aliment Pharmacol Ther. 2015;41:262–75.