Oral immunotherapy for food allergy

Abstract

Food allergy is an increasingly prevalent disorder with potentially life-threatening complications that requires life-altering changes in dietary habits and psychosocial interactions. The standard of care presently includes strict dietary elimination of the implicated allergen and ready access to injectable epinephrine; however, no active, definitive therapeutic options exist for food-allergic patients. Although the detailed immunologic mechanisms underlying the development of food allergy are still being fully defined, food allergy appears to be the direct result of a breakdown in oral tolerance. Thus, current therapeutic approaches to food allergy are focused on modulating the immunologic response to food proteins to promote induction of oral tolerance. In this review, we examine gastrointestinal mucosal immunity and the mechanisms of oral tolerance, as well as the breakdown in oral tolerance that promotes food allergy, and we also explore novel therapeutic interventions for treatment of food allergy.

Mucosal immunity in a healthy gut

“…As alluded to above, oral tolerance appears as a robust adaptive immune function because even healthy adults absorb measurable concentrations of intact food antigens, particularly after meals -corresponding to 10 -5 of the intake and reaching a circulating level of 3-10 ng/ml 27 -thus representing a small fraction of the total daily protein uptake which perhaps amounts to 130-190 g. 28 The epithelial tightness and the immunoregulatory network remain fragile for a variable period after birth. 29,30 Importantly, animal experiments show that the postnatal development of mucosal homeostasis depends on the establishment of a balanced commensal microbiota as well as adequate timing and dosing of dietary antigens when first introduced.…”

Extensively heated milk and egg as oral immunotherapy

“…In food oral immunotherapy trials, side-effects include but are not limited to oral pruritus, respiratory symptoms, gastrointestinal symptoms such as abdominal discomfort, emesis and diarrhea, as well as reactions requiring the use of epinephrine [31][32][33][34][35][36][37][38][39][40][41][42]. The potential for the development of eosinophilic gastrointestinal disease such as eosinophilic esophagitis (EoE) is also a concern [35].…”

Oral immunotherapy for cow's milk allergy

“…In fact, in the available literature (see below), although usually patients have ascertained IgE-mediated CMA, the immunological changes were investigated less in depth than for aeroallergen immunotherapy, the induction protocols were largely variable, and long-term data are few. Moreover, it is still unclear whether oral desensitization is only the first step toward permanent desensitization or it induces only a transient tolerance [20]. On the other hand, in westernized countries and in real life, the continuous or frequent ingestion of foods, such as cow's milk or hen's egg, after the achievement of desensitization is per se easy to do by patients.…”