Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures.
Crohn's disease
PhIP-Seq
antibody repertoire
antibody response
epitopes
flagellins
gut microbiota
inflammatory bowel disease
ulcerative colitis
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
13 06 2023
13 06 2023
Historique:
received:
07
12
2021
revised:
13
12
2022
accepted:
14
04
2023
medline:
16
6
2023
pubmed:
11
5
2023
entrez:
10
5
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37164015
pii: S1074-7613(23)00185-1
doi: 10.1016/j.immuni.2023.04.017
pii:
doi:
Substances chimiques
Antibodies
0
Epitopes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1393-1409.e6Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests G.D. received an unrestricted research grant from Takeda and speaker fees from Pfizer and Janssen Pharmaceuticals. R.K.W. 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. M.C.V. received speaker fees from Janssen-Cilag, Galapagos, and Ferring B.V.