Induction of tolerance to food allergens—Younger is better

Durable tolerance, or the ability to safely tolerate allergen ingestion through preventative intervention or modulation of an existing immunoglobulin E (IgE)-mediated food allergy, is vital to the treatment of food allergy. Recent insights through clinical trials and fundamental research have discovered that interventions at younger ages underlie higher frequency and durability of tolerance after treatment. Here, we review highly successful preventive and clinical trials of oral, sublingual, and epicutaneous immunotherapy for food allergy and the evidence that intervention at a younger age is highly successful at the induction of durable tolerance. In parallel, our ability to interrogate the mechanisms of IgE-mediated food allergy has become increasingly sophisticated. Work on IgE diversity has repeatedly established that greater IgE diversity and immune progression with time are associated with poorer clinical outcomes. Durable tolerance, on the other hand, is associated with neutralizing antibodies that block multiple IgE clones, thereby providing protection from a diversified IgE repertoire. Taken together, these advances not only pave an evidence-based pathway for the treatment of IgE-mediated food allergies but also help us understand the mechanism of these interventions, allowing us for the first time to begin to address the wide range of heterogeneity underlying IgE-mediated food allergy to advance therapeutic implementation.