New Insights in Therapy for Food Allergy

Abstract

Food allergy is an increasing problem worldwide, with strict avoidance being classically the only available reliable treatment. The main objective of this review is to cover the latest information about the tools available for the diagnosis and treatment of food allergies. In recent years, many efforts have been made to better understand the humoral and cellular mechanisms involved in food allergy and to improve the strategies for diagnosis and treatment. This review illustrates IgE-mediated food hypersensitivity and provides a current description of the diagnostic strategies and advances in different treatments. Specific immunotherapy, including different routes of administration and new therapeutic approaches, such as hypoallergens and nanoparticles, are discussed in detail. Other treatments, such as biologics and microbiota, are also described. Therefore, we conclude that although important efforts have been made in improving therapies for food allergies, including innovative approaches mainly focusing on efficacy and safety, there is an urgent need to develop a set of basic and clinical results to help in the diagnosis and treatment of food allergies.

Keywords: food allergy; hypoallergens; microbiota; nanoparticles; non-specific therapy; specific immunotherapy.

Figure 1

Immunological mechanisms involved in FA: (A) Food allergens are taken up by the DC and presented to Th0 cells. ILC2 have been described as IL-5 and IL-13 producers, promoting Th2 response. These cells differentiate into Th2 cells, releasing type-2 cytokines and promoting B cell differentiation into IgE-producing plasma cells. (B) Food allergen-sIgE binds to FCεR placed on mast cells. Re-exposure to specific food allergen induces mast cell degranulation and promotes Th2 immune response.

Figure 2

Cellular mechanisms involved in allergen-specific immunotherapy (ASIT) and non-allergen-specific therapy (NAIT). Different therapies exist in the ASIT, such as OIT, SLIT, and EPIT, and in the NAST such as biologics and microbiota. The cellular mechanism in the ASIT implies low doses of food allergen favoring regulatory responses, with Treg cell proliferation, an immunosuppressive Th2 cytokine production, and an immune activation of the Th1 cytokine production to restore the Th1/Th2 balance. All this decreases the production of allergen-sIgE. On the other hand, NAST using biologics directly blocks IgE (omalizumab) or cytokines involved in the Th2 response (dupilumab and etokimab), avoiding cell signaling and all underlying processes involved in FA. In the same way, microbiota acts on the Treg cells by favoring the release of immunosuppressive cytokines (IL-10) as well as plasma cells increasing the immunoglobulin G (IgG)₄/IgE ratio.