Identification of an Anti-Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis.
Adult
Aged
Aged, 80 and over
Antigens, Neoplasm
/ immunology
Autoantibodies
/ blood
Biomarkers
/ blood
Case-Control Studies
Cell Adhesion
/ immunology
Colitis, Ulcerative
/ blood
Colon
/ immunology
Enzyme-Linked Immunosorbent Assay
Female
Fluorescent Antibody Technique
Humans
Immunoprecipitation
Integrins
/ immunology
Male
Middle Aged
Sensitivity and Specificity
Severity of Illness Index
Young Adult
Autoimmunity
Epithelial Adhesion Molecule
Inflammatory Bowel Disease
RGD Motif
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
27
03
2020
revised:
12
01
2021
accepted:
09
02
2021
pubmed:
15
2
2021
medline:
12
1
2022
entrez:
14
2
2021
Statut:
ppublish
Résumé
Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti-integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti-integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6-fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity.
Sections du résumé
BACKGROUND AND AIMS
Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated.
METHODS
Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays.
RESULTS
Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti-integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti-integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6-fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion.
CONCLUSIONS
A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity.
Identifiants
pubmed: 33582126
pii: S0016-5085(21)00406-6
doi: 10.1053/j.gastro.2021.02.019
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Autoantibodies
0
Biomarkers
0
Integrins
0
integrin alphavbeta6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2383-2394.e21Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.