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
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.e6

Informations 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.

Auteurs

Arno R Bourgonje (AR)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Sergio Andreu-Sánchez (S)

Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Thomas Vogl (T)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University Graz, Graz, Austria; Center for Cancer Research, Medical University of Vienna, Wien, Austria.

Shixian Hu (S)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Arnau Vich Vila (A)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Ranko Gacesa (R)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Sigal Leviatan (S)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Alexander Kurilshikov (A)

Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Shelley Klompus (S)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Iris N Kalka (IN)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Hendrik M van Dullemen (HM)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Adina Weinberger (A)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Marijn C Visschedijk (MC)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Eleonora A M Festen (EAM)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Klaas Nico Faber (KN)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Cisca Wijmenga (C)

Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Gerard Dijkstra (G)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Eran Segal (E)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Jingyuan Fu (J)

Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Alexandra Zhernakova (A)

Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Rinse K Weersma (RK)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: r.k.weersma@umcg.nl.

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