IgE and non-IgE food allergy: A review of immunological mechanisms

Abstract

Background: Food allergic (FA) conditions have been classified as immunoglobulin E (IgE) and non-IgE‐mediated reactions that affect as many as 8% of young children and 2% of adults in Western countries, and their prevalence seems to be rising. Although the immunologic basis of IgE-mediated FA is well established, the mechanisms that govern non-IgE‐mediated FA are not well understood and are marked by a paucity of comprehensive insights. Objective: The purpose of the present report is to examine the current classification and epidemiology of non-IgE‐mediated FA, the latest immunologic mechanisms that underlie the three most commonly cited non-IgE FA conditions, viz., eosinophilic esophagitis, food protein-induced enterocolitis, and food protein‐induced allergic proctocolitis, and explore what allergist/immunologists in practice should be aware of with regard to the condition. Methods: An extensive research was conducted in medical literature data bases by applying terms such as FA, non-IgE allergy, tolerance, unresponsiveness, cytokines, CD4+ T helper cell pathways, and key cytokine pathways involved in FA. Results: Current evidence now supports the view that immune dysregulation and cytokine-induced inflammation are the fundamental bases for both IgE- and non-IgE‐mediated FA. The existing non-IgE‐related FA literature is mostly characterized by a relative dearth of mechanistic information in contrast to IgE-mediated FA, in which the immunologic underpinnings as a T helper type 2 directed entity are well established. Although the need for future methodologic research and adherence to rigorous scientific protocols is essential, it is also necessary to acknowledge past contributions that have given much to our understanding of the condition. In the present report, a novel signature cytokine-based classification of IgE-mediated and non-IgE‐mediated allergy is proposed that may offer a novel template for future research in the field of non-IgE‐mediated FA. Conclusion: The present report provides an overview of the current classification and frequency of IgE‐ and non-IgE‐mediated FAs, and offers insights and potential solutions to address lingering questions, particularly when concerning the latest immunologic mechanisms that underlie the pathogenesis of non-IgE-mediated FA. Although some progress has been made in recent years toward making diagnostic and treatment options available for these conditions, there still remain many lingering questions and concerns to be addressed, which can be fully understood by future research.