Mechanisms of Tolerance Induction

Abstract

Food allergy results from failure in oral tolerance that usually occurs in infancy or early childhood. Exposure to peanut and hen's egg via the inflamed and disrupted epithelial barrier in children with severe atopic dermatitis is a risk factor for the development of allergy to these foods and supports the hypothesis that epicutaneous exposure in the absence of oral feeding is an important pathway of allergic IgE sensitization in infants. In recent years, the collective evidence has pointed toward the protective effect of an early feeding with peanut and egg in children with eczema, taking advantage of the pathways underlying oral tolerance to counteract epicutaneous exposure. An addendum to the NIAID food allergy guidelines recommends introduction of peanut into the diet of 4- to 6-month-old infants with severe eczema or egg allergy as an effective strategy to prevent peanut allergy. Strategies aimed at restoring the skin barrier are currently explored as an alternative approach of prevention of eczema and allergic sensitization. Manipulation of the diet via supplementation with probiotics and prebiotics to restore the healthy gut microbiota represents another potential pathway to induction of tolerance in the gut. Oral, epicutaneous, and sublingual routes of food immunotherapy are promising and induce desensitization in the majority of the treated subjects with food allergy but are not proven to restore permanent oral tolerance. Rigorous multicenter randomized clinical trials are necessary to elucidate the optimal timing, dose, duration, as well as the preventive and therapeutic effects of these diverse approaches.