Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures

Arno R. Bourgonje, Sergio Andreu-Sánchez, Thomas Vogl, Shixian Hu, Arnau Vich Vila, Ranko Gacesa, Sigal Leviatan, Aleksandr Kurilshchikov, Shelley Klompus, Iris N. Kalka, Hendrik M. van Dullemen, Adina Weinberger, Marijn C. Visschedijk, Eleonora A. M. Festen, Klaas Nico Faber, Cisca Wijmenga, Gerard Dijkstra, Eran Segal, Jingyuan Fu, Alexandra ZhernakovaRinse K. Weersma

OnderzoeksoutputAcademicpeer review

1 Citaat (Scopus)


Inflammatory bowel diseases (IBDs), 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. Using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq), we identified antibodies against 344,000 antimicrobial, immune, and food antigens in 497 individuals with IBD compared with 1,326 controls. IBD was characterized by 373 differentially abundant antibody responses (202 overrepresented and 171 underrepresented), with 17% shared by both IBDs, 55% unique to CD, and 28% unique to UC. Antibody reactivities 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 (area under the curve [AUC] = 0.89), and similar discrimination was achieved when using only ten antibodies (AUC = 0.87). Individuals with IBD thus show a distinct antibody repertoire against selected peptides, allowing clinical stratification and discovery of immunological targets.
Originele taal-2English
Aantal pagina's24
Nummer van het tijdschrift6
StatusE-pub ahead of print - 9-mei-2023

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