Evolution of Epitope-specific IgE and IgG4 Antibodies in Children Enrolled in the LEAP Trial.

Abstract Background In the Learning Early About Peanut Allergy (LEAP) trial, early consumption of peanut in high-risk infants was found to decrease the rate of peanut allergy at 5 years of age. Sequential epitope-specific (ses-)IgE is a promising biomarker of clinical peanut reactivity. Objective To compare the evolution of ses-IgE and ses-IgG4 in children who developed (or not) peanut allergy, and to evaluate the immunomodulatory effects of early peanut consumption on these antibodies. Methods Sera from 341 children (LEAP cohort) were assayed at baseline, 1, 2.5 and 5 years of age, with allergy status determined by oral food challenge at 5 years. A bead-based epitope assay was used to quantitate ses-IgE and ses-IgG4 to 64 sequential epitopes from Ara h 1-3, and analyzed using linear mixed-effect models. Results In children avoiding peanut who became peanut allergic, the bulk of peanut ses-IgE did not develop until after 2.5 years. Minimal increases of ses-IgE occurred after 1 year in consumers, but not to the same epitopes as children developing peanut allergy. No major changes in ses-IgE were seen in non-allergic or sensitized children. IgE in sensitized consumers was detected against peanut proteins. Ses-IgG4 increased over time in most children regardless of consumption or allergy status. Conclusion Early peanut consumption in infants at high risk of developing peanut allergy appears to divert the immunologic response to a presumably “protective” effect. In general, consumers tend to generate ses-IgG4 earlier and in greater quantities than non-consumers, whereas only avoiders tend to generate significant quantities of ses-IgE.