Desensitizing Food Allergies Using Allergenic Molecules

Abstract and Introduction

Abstract

Purpose of review Food allergy has risen in prevalence worldwide and is one of the main causes of anaphylaxis, especially in children. The only possible therapeutic approach is specific immunotherapy. This review describes the recent approaches using allergenic molecules for specific immunotherapy.

Recent findings Hypoallergenic tropomyosins from Metapenaeus ensis have been cloned and constructed by direct mutagenesis or epitope deletion and have been successfully used in shrimp-sensitized mice. A modified carp parvalbumin is being used in phase I/IIa clinical trials in patients with fish allergy. Natural lipid transfer protein (Pru p 3) and profilin (Pho d 2) extracts have been used for the treatment of patients with plant food allergy. Treatments of egg-sensitized mice with glycated-ovalbumin and ovomucoid peptides led to a clinical and immunological improvement. A preventive treatment with synthetic β-lactoglobulin peptides was effective in reducing skin symptoms in mice sensitized to milk whey proteins but no dominant epitopes were found in α-lactalbumin. Finally peanut desensitization has been attempted using three modified recombinant peanuts but the protocol was interrupted and limited to a phase 1 study because of side-effects.

Summary Many molecules, including allergenic peptides or modified proteins are under consideration but clinical trials in food-allergic study participants are necessary to confirm tolerability and efficacy.

Introduction

Food allergy is defined as an adverse, reproducible immune-mediate response to a given food. The term allergy encompasses both IgE-mediated and non-IgE-mediated reactions.

Every food can be responsible for an allergic reaction but the great majority of allergic reactions are provoked by peanut, tree nuts, seafood, cow milk, egg, wheat, soy, fruits/vegetables (often because of cross-reactivity with pollens), and seeds. According to various studies, food allergy affects about 5% of adults and 8% of children in western countries and its prevalence has increased in the last few decades. Cow milk, egg, peanut, tree nuts, soybean, wheat, and seafood are the main responsible of food allergy in children. In adults, peanut, tree nuts, seafood, and fruit/vegetables are the most important food allergens.^[1,2]

The rate of IgE-mediated allergy resolution varies according mainly to the food and the patient's age (milk and egg allergy have a higher resolution rate than peanut within the first 5 years of life).^[3] Current management of food allergy is based on food avoidance and recognition and treatment of allergic reactions but food avoidance is not always possible because of the presence of hidden allergens and may affect patients' quality of life and/or their nutritional status. For these reasons since the 1980s researchers have paid attention to oral food-specific immunotherapy (SIT) to treat food-allergic patients.^[4] The exact mechanisms of food immunotherapy are still not known but immunologic changes include decreased reactivity of mast cells and basophils, increased food-specific IgG4 and increased regulatory T cells (Tregs). Tregs suppress Th2-immune response via secretion of IL-10 and/or TGFβ. The development of Tregs is responsible for permanent tolerance (or long-term desensitization).^[5]

The great majority of published studies deal with food oral immunotherapy (OIT) with whole foods but recently some authors have paid attention also to sublingual immunotherapy (SLIT) and epicutaneous immunotherapy. Subcutaneous immunotherapy (SCIT) has been attempted in the past but has been abandoned because of side-effects.^[6–12]

The purpose of this review is to provide an update on the possibility to use recombinant or native major allergenic molecules to treat food allergic patients.