Oral immunotherapy as a curative treatment for food-allergic preschool children: Current evidence and potential underlying mechanisms

The worldwide rising prevalence of food allergy is a major public health concern. Standard care consists of allergen avoidance and rescue medication upon accidental exposure. Oral immunotherapy (OIT) is increasingly being studied as a treatment option. Although desensitization (an increased reaction threshold) is often achieved during OIT, sustained unresponsiveness (SU; clinical nonreactivity after finishing OIT) is not achieved in most patients. A few studies have investigated the effectiveness of OIT in children younger than 4 years of age (early = e-OIT) and have shown a much more favorable outcome in terms of SU development. Together with food allergy prevention studies, which have demonstrated high efficacy of early oral allergen exposure, the outcomes of e-OIT studies indicate an early-life window of opportunity to achieve SU, allowing unrestricted dietary intake. However, the underlying mechanism of the high effectiveness of e-OIT is not understood yet. Both cohort and OIT studies indicate early-life immune plasticity. An immature food-allergic response in the first years of life seems to be a major driver of this immune plasticity, along with a higher tolerogenic immunological state. Allergy maturation can likely be disrupted effectively by early intervention, preventing the development of persistent food allergy. Upcoming studies will provide important additional data on the safety, feasibility, and effectiveness of e-OIT. Combined with immune mechanistic studies, this should inform the implementation of e-OIT.