IgE-Induced Food Allergy

What Is Food Allergy?

Food allergy is defined differently from food intolerance, which is generally defined as a non-immune response that includes metabolism, toxicity, pharmacology, and a number of unidentified mechanisms, whereas food allergy is defined as an adverse immune response to food proteins. Immune-mediated food allergy may result in the induction of enteropathy in patients and may also present with conditions such as acute urticaria, atopic dermatitis, and allergic contact dermatitis. Celiac disease triggered by gluten in food is generally not categorized as a food allergy disorder.

The manifestations of food allergy vary greatly depending on the immune mechanisms involved and the target organs affected, ranging from the typical acute urticaria to chronic conditions such as eczema or eosinophilic gastrointestinal disease. A combination of clinical symptoms and laboratory tests is required to accurately diagnose the type of disease.

Figure 1. Classification of adverse reactions to food
(Source: Sampson HA, et al. 2014)

Pathogenesis of Food Allergy

IgE-mediated food allergy is the result of loss of integrity of key immune components that maintain tolerance and prevent recognition of benign food antigens as pathogens. Tolerance to food is the process by which food antigens cross the mucosal barrier and are processed by dendritic cells in their inactivated state, and these antigen-presenting cells also induce inhibitory cytokines such as IL-10. This, in turn, leads to differentiation of naïve T cells into T regulatory cells, suppression of food antigen-specific T helper 2 (Th2) cells, and increased production of IgA and IgG4 and decreased production of IgE by B cells. Eosinophils, basophils and mast cells are immunosuppressed.

A state of detectable food-specific IgE is defined as sensitization, which may be a precursor to the development of food allergy. When food passes through the broken barrier, danger signals and inflammatory cytokines are released, which activates dendritic cells to form a phenotype normally acquired in defense against pathogens. These activated dendritic cells, in turn, activate naïve T cells to acquire a Th2 phenotype, which in turn promotes inflammatory signaling, induces food antigen-specific B cells to undergo class switching and produce food antigen-specific IgE. All patients with IgE-mediated food allergy are allergic to food allergens. The development of a food allergic reaction consists of five key components: epithelial cells, innate immune cells, T cells, B cells, and effector cells (mast cells, eosinophils, and basophils).

Figure 2. Comparative overview of the tolerogenic versus allergic response to food antigen in the gut
(Source: Anvari S, et al. 2019)

Diagnosis of Food Allergy

IgE-mediated food allergy testing initially relied on taking a history and physical examination, however, this diagnostic method is not highly accurate. The double-blind placebo-controlled food test (DBPCFC) is the gold standard for diagnosing food allergy in clinical trials or standardized studies. Oral food challenge can definitively diagnose IgE-mediated food allergy, but requires clinicians who can quickly recognize and treat food allergy. Patients need to be evaluated prior to testing for the presence of comorbidities such as asthma, uncontrolled urticaria or eczema, or concurrent respiratory infections, which carry the risk of exposing the patient to a serious and fatal reaction. During the test, patients should first eat a very small amount of food and increase the dose every 15-30 minutes until all steps are completed or symptoms appear. In addition, when preparing for an oral challenge, patients should stop taking antihistamines or corticosteroids that may interfere with the outcome of the challenge.

Commonly used methods for detecting IgE-induced food allergies include the immediate hypersensitivity skin test (IHST) and the food-specific IgE antibody test. It is important to note that patients who have already had an allergic reaction need to wait 4-6 weeks before undergoing skin testing. The IHST rapidly screens for the presence of food-specific IgE antibodies on skin mast cells. The test is performed using a device coated with a commercial extract or fresh food, which is scraped against the skin surface, allowing food proteins to enter the skin, bind to specific IgE on skin mast cells and trigger a degranulation reaction with preformed mediators such as histamine. Local mast cells are activated to produce visualized wheals and erythema at the site of allergen entry through the skin, with the diameter of the wheals providing information on the likelihood of a clinical reaction. Skin test results were positive if the mean diameter of the wheal was ≥ 3 mm compared with negative controls. However, the food skin test has a low specificity, does not distinguish between sensitization and true IgE-mediated allergic reactions, and is not directly diagnostic of clinical reactivity.

Food Allergen ELISA Kits

Food Allergen Antigens

Food Allergen Antibodies