Scientific Study

Background: The development and resolution of peanut allergy (PA) was evaluated in children enrolled or screened for the LEAP intervention trial. The development of epitope-specific-immunoglobulin(es-Ig)E and es-IgG4 antibodies was evaluated in a subset of these children to determine whether their PA status could be predicted at 4-11 months of age. Methods: Sera from 386children enrolled or screened as part of the LEAP trial were assayed at 4-11 months (baseline) and 60 months of age, and final allergy status was established by OFC at 60 months. Es-IgE and es-IgG4 to 64 informative peanut epitopes were analyzed using linear mixed-effect models and Machine Learning (ML) was used to develop a predictive algorithm. Results: Children were categorized in four groups: 37 developed PA early that persisted (EP), 17 developed PA early but resolved (ER), 33 developed PA later in childhood (by 60 months of age, LA), and 298 never developed PA (NA). Differences among groups in es-IgE and es-IgG4 were detectable at baseline. ER showed lower levels of Ara h 2_008 es-IgE and higher es-IgG4 levels to several epitopes compared to the EP group. Both EP and ER groups had greater levels of several baseline es-IgE antibodies compared to the LA. By 60 months, all three groups had significant increases in both the levels and diversity of es-IgG4 antibodies, while es-IgE antibodies increased only in EP and LA groups and decreased in ER group. ML models were predictive of persistent allergy by 60 months of age with an average AUC in testing of 0.75. Conclusions: These results suggest that baseline es-IgE in children sensitized in the first year of life can predict likely persistent peanut allergy. Clinical implications: Evaluation of es-IgE antibodies in the first year of life is useful for identifying infants who will develop persistent peanut allergy and in whom early treatment should be prioritized.

https://doi.org/10.1016/j.jaci.2025.06.022