Molecular characterization of the IgE serological repertoire in pediatric peanut allergy 2267488

Abstract Introduction Though recent strides in peanut allergy prevention have changed the clinical thinking about pediatric treatment, the antibodies responsible for severe allergic reactions, IgE, remain poorly understood, especially at the molecular level. The advent of BCR-seq–deep sequencing of the B cell receptor (BCR) repertoire–has illuminated molecular features of pathogenic IgE producing B cells causing food allergies. However, the degree to which the transcribed BCR repertoire represents the circulating secreted immunoglobulin (Ig) repertoire is not known. Methods Here, we use parallel BCR- and Ig-seq methods to describe the circulating IgE, IgG, and IgA repertoires in pediatric donors with peanut allergy. Results Tandem liquid chromatography mass spectrometry allows for relative quantitation of serological lineages, identification of CDRH3 motifs underlying peanut allergy, description of antibody clone convergence, and analysis of lineage overlap between circulating isotypes. Conclusion Because the correlation between peanut-specific IgE and peanut allergy is weak, comprehensive characterization of the IgE serological repertoire will inform diagnostic opportunities as well as elucidate mechanisms underlying B cell and Ig trafficking in food-allergic individuals. To our knowledge, this is the first molecular-level proteomic IgE repertoire analysis completed. Funding Source Texas Biologics Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)