DOP53 In-depth characterisation of the serum antibody epitope repertoire in Inflammatory Bowel Disease by high-throughput phage-displayed immunoprecipitation sequencing

Abstract

Inflammatory bowel diseases (IBD), e.g. Crohn’s disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases. A comprehensive overview of an IBD-specific antibody epitope repertoire is, however, lacking. We leveraged a high-throughput phage-displayed immunoprecipitation sequencing (PhIP-seq) workflow to identify antibodies against 344,000 antimicrobial, immune and food antigens in 497 IBD patients as compared to 1,326 controls. IBD was characterized by 373 differentially abundant antibodies (202 overrepresented and 171 underrepresented), with 17% shared by both IBDs, 55% unique to CD and 28% unique to UC. Antibodies against bacterial flagellins dominated in CD and were associated with ileal involvement, fibrostenotic disease and anti-Saccharomyces cerevisiae antibody positivity, but not with fecal microbiome composition. Antibody epitope repertoires accurately discriminated CD from controls (AUC=0.89), and similar discrimination was achieved when using only ten antibodies (AUC=0.87). IBD patients thus show a distinct antibody repertoire against selected peptides, allowing patient stratification and discovery of immunological targets.Competing Interest StatementGD received an unrestricted research grant from Takeda and speaker fees from Pfizer and Janssen Pharmaceuticals. RKW acted as consultant for Takeda, received unrestricted research grants from Takeda, Johnson & Johnson, Tramedico and Ferring and received speaker fees from MSD, Abbvie and Janssen Pharmaceuticals. All other authors declare no competing interests.