Introduction to Special Issue on Food Allergy

This special issue of Seminars in Immunopathology reviews recent progress in our understanding of food allergy. Foodsensitive enteropathies can be defined as reproducible clinical response(s) to a given food (or foods) that are governed by an aberrant (typically Th2-mediated) immune response. Pathological responses to innocuous food antigens can be both IgEand non-IgE-mediated. This volume will focus primarily on the IgE-mediated anaphylactic reactions to food that are a growing public health concern in westernized countries [1]. Food allergies are increasingly common, especially in children. In the USA three million children (four out of every 100) were reported to have an allergic response to food in 2007, an increase of almost 20 % in just 10 years [2]. Similar trends have been reported in the UK [3] and in Australia [4]. Several reports indicate that, in the USA, allergic responses to food are the most frequent cause of anaphylactic reactions evaluated in the emergency room [5, 6]. For reasons that are not yet clear, 90 % of hypersensitivity reactions are attributable to only eight major types of food: milk, eggs, shellfish (particularly crustaceans), peanuts, soybeans, tree nuts, and wheat. Allergic responses to milk, soybeans, eggs, and wheat are typically transient and restricted to childhood; while peanuts, tree nuts, and shellfish are more likely to induce life-long anaphylactic hyperreactivity. In the first article in this issue, Ruiter and Shreffler discuss the molecular basis for allergenicity. Helminths and allergens uniquely induce Th2-biased immune responses. The authors review the literature on innate Th2 immune activation to glean novel insights into the immunogenic properties of food allergens. The allergic effector response is mediated by IgE, most commonly considered in the context of the mast cell cross-linking and degranulation induced by binding to its high-affinity receptor FceR1. However, as discussed by Berin, each of the three isotypes of immunoglobulin present at mucosal surfaces play a particular role in promoting tolerance or immunity to foods by facilitating antigen uptake. IgA, the dominant isotype, is secreted into the lumen and acts to prevent allergen from crossing the epithelial barrier. Antigen-specific IgA levels inversely correlate with clinical reactivity to food and aeroallergens. Conversely, IgG contributes to non-responsiveness to dietary antigen by facilitating antigen sampling. The neonatal Fc receptor transports antigen: IgG complexes from breast milk to induce tolerance to potential allergens early in life. By contrast, IgE-facilitated antigen delivery via CD23 contributes to clinical reactivity by delivering antigen:IgE complexes to allergic effector cells [7]. Food allergic patients do not present with a consistent set of complaints. Symptoms can range from transient urticaria or extend beyond the skin and gastrointestinal tract to the respiratory and cardiovascular collapse characteristic of a systemic anaphylactic response. Only some foods seem to trigger anaphylaxis; peanuts and tree nuts most commonly induce severe reactions, but there is currently no way to predict what kind of response will occur. A better understanding of allergic effector pathways may be helpful in predicting disease severity. Based on both murine model data and corroborative human studies, Hogan et al. suggest that intestinal mast cells play an important role in controlling the severity of food-induced anaphylaxis [8]. Two possible scenarios are presented: intestinal mast cells may lead to increased intestinal permeability and systemic antigen absorption, enabling systemic mast cell activation and potentiation of respiratory and cardiovascular collapse. Alternatively, in the presence of high intestinal mast cell numbers, mediators released in response to mast cell degranulation in the intestine may gain access to the systemic circulation and stimulate respiratory and cardiovascular collapse directly. This article is published as part of the Special Issue on Food Allergy [34:5].