Kinetics of epitope-specific IgE and IgG₄ in early peanut allergy development and resolution.

Abstract

The development and resolution of peanut allergy (PA) was evaluated in children enrolled or screened for the Learning Early About Peanut (LEAP) intervention trial. The development of epitope-specific (es) IgE 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. Sera from 386 children 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 oral food challenge at 60 months. Es-IgE and es-IgG₄ to 64 informative peanut epitopes were analyzed by linear mixed-effect models, and machine learning was used to develop a predictive algorithm. Children were categorized in 4 groups: 37 developed PA early that persisted (EP), 17 developed PA early that resolved (ER), 33 developed PA later in childhood (by 60 months of age, LA), and 298 never developed PA. 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 group. By 60 months, all 3 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. Machine learning models were predictive of persistent allergy by 60 months of age, with an average area under the curve in testing of 0.75. These results suggest that baseline es-IgE in children sensitized in the first year of life can predict likely persistent PA.