TY - JOUR
T1 - Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures
AU - Bourgonje, Arno R.
AU - Andreu-Sánchez, Sergio
AU - Vogl, Thomas
AU - Hu, Shixian
AU - Vich Vila, Arnau
AU - Gacesa, Ranko
AU - Leviatan, Sigal
AU - Kurilshchikov, Aleksandr
AU - Klompus, Shelley
AU - Kalka, Iris N.
AU - van Dullemen, Hendrik M.
AU - Weinberger, Adina
AU - Visschedijk, Marijn C.
AU - Festen, Eleonora A. M.
AU - Faber, Klaas Nico
AU - Wijmenga, Cisca
AU - Dijkstra, Gerard
AU - Segal, Eran
AU - Fu, Jingyuan
AU - Zhernakova, Alexandra
AU - Weersma, Rinse K.
PY - 2023/5/9
Y1 - 2023/5/9
N2 - 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.
AB - 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.
U2 - 10.1016/j.immuni.2023.04.017
DO - 10.1016/j.immuni.2023.04.017
M3 - Article
SN - 1074-7613
VL - 56
JO - Immunity
JF - Immunity
IS - 6
ER -