Human Microbiota Flagellins Drive Adaptive Immune Responses in Crohn's Disease.
Adaptive Immunity
Adult
Aged
Aged, 80 and over
Antibodies, Bacterial
/ blood
Antigens, Bacterial
/ immunology
B-Lymphocytes
/ immunology
CD4-Positive T-Lymphocytes
/ immunology
Case-Control Studies
Clostridiales
/ immunology
Colitis, Ulcerative
/ blood
Crohn Disease
/ blood
Cross-Sectional Studies
Female
Flagellin
/ immunology
Humans
Immunoglobulin A
/ blood
Immunoglobulin G
/ blood
Male
Middle Aged
Young Adult
Adaptive Immunity
Crohn’s Disease
Flagellin
Microbiota
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
20
10
2020
revised:
26
03
2021
accepted:
30
03
2021
pubmed:
13
4
2021
medline:
19
1
2022
entrez:
12
4
2021
Statut:
ppublish
Résumé
Crohn's disease and ulcerative colitis are characterized by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals, but the specificity of these responses remains largely undefined. Therefore, we developed a microbiota antigen microarray to characterize microbial antibody reactivity, particularly to human-derived microbiota flagellins, in inflammatory bowel disease. Sera from healthy volunteers (n = 87) at the University of Alabama at Birmingham and from patients recruited from the Kirklin Clinic of University of Alabama at Birmingham Hospital, including patients with Crohn's disease (n = 152) and ulcerative colitis (n = 170), were individually probed against microbiota bacterial flagellins of both mouse and human origin and analyzed for IgG and IgA antibody responses. Circulating flagellin-reactive T effector (CD4 We show that patients with IBD express selective patterns of antibody reactivity to microbiota flagellins. Patients with Crohn's disease, but not patients with ulcerative colitis, display augmented serum IgG to human ileal-localized Lachnospiraceae flagellins, with a subset of patients having high responses to more than 10 flagellins. Elevated responses to CBir1, a mouse Lachnospiraceae flagellin used clinically to diagnose CD, correlated with multi-Lachnospiraceae flagellin reactivity. In this subset of patients with CD, multi-flagellin reactivity was associated with elevated flagellin-specific CD154 Patients with Crohn's disease display strong adaptive immune response to human-derived Lachnospiraceae flagellins, which may be targeted for prognosis and future personalized therapies.
Sections du résumé
BACKGROUND AND AIMS
Crohn's disease and ulcerative colitis are characterized by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals, but the specificity of these responses remains largely undefined. Therefore, we developed a microbiota antigen microarray to characterize microbial antibody reactivity, particularly to human-derived microbiota flagellins, in inflammatory bowel disease.
METHODS
Sera from healthy volunteers (n = 87) at the University of Alabama at Birmingham and from patients recruited from the Kirklin Clinic of University of Alabama at Birmingham Hospital, including patients with Crohn's disease (n = 152) and ulcerative colitis (n = 170), were individually probed against microbiota bacterial flagellins of both mouse and human origin and analyzed for IgG and IgA antibody responses. Circulating flagellin-reactive T effector (CD4
RESULTS
We show that patients with IBD express selective patterns of antibody reactivity to microbiota flagellins. Patients with Crohn's disease, but not patients with ulcerative colitis, display augmented serum IgG to human ileal-localized Lachnospiraceae flagellins, with a subset of patients having high responses to more than 10 flagellins. Elevated responses to CBir1, a mouse Lachnospiraceae flagellin used clinically to diagnose CD, correlated with multi-Lachnospiraceae flagellin reactivity. In this subset of patients with CD, multi-flagellin reactivity was associated with elevated flagellin-specific CD154
CONCLUSIONS
Patients with Crohn's disease display strong adaptive immune response to human-derived Lachnospiraceae flagellins, which may be targeted for prognosis and future personalized therapies.
Identifiants
pubmed: 33844987
pii: S0016-5085(21)00633-8
doi: 10.1053/j.gastro.2021.03.064
pmc: PMC8489510
mid: NIHMS1692729
pii:
doi:
Substances chimiques
Antibodies, Bacterial
0
Antigens, Bacterial
0
Immunoglobulin A
0
Immunoglobulin G
0
Flagellin
12777-81-0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
522-535.e6Subventions
Organisme : CSRD VA
ID : I01 CX001530
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007051
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.
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