TLR9 signalling in HCV-associated atypical memory B cells triggers Th1 and rheumatoid factor autoantibody responses.
Autoantibodies
/ immunology
Autoimmunity
B-Lymphocytes
/ immunology
Cells, Cultured
Cryoglobulinemia
/ etiology
Female
Hepacivirus
/ immunology
Hepatitis C, Chronic
/ complications
Humans
Immunoglobulin M
/ immunology
Immunologic Memory
Lymphocyte Activation
Male
Middle Aged
Receptors, Complement 3d
/ metabolism
Rheumatoid Factor
/ immunology
Signal Transduction
/ immunology
Th1 Cells
/ immunology
Toll-Like Receptor 9
/ metabolism
Transcriptome
Tumor Necrosis Factor Receptor Superfamily, Member 7
/ metabolism
Atypical memory B cells
Cryoglobulinemia vasculitis
Hepatitis C virus
Immunology, direct-acting antiviral
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
30
10
2018
revised:
24
06
2019
accepted:
27
06
2019
pubmed:
8
7
2019
medline:
22
12
2020
entrez:
8
7
2019
Statut:
ppublish
Résumé
Hepatitis C virus (HCV) infection contributes to the development of autoimmune disorders such as cryoglobulinaemia vasculitis (CV). However, it remains unclear why only some individuals with HCV develop HCV-associated CV (HCV-CV). HCV-CV is characterized by the expansion of anergic CD19 The phenotype and function of peripheral AtMs were studied by multicolour flow cytometry and co-culture assays with effector T cells and regulatory T cells in 20 patients with HCV-CV, 10 chronicallyHCV-infected patients without CV and 8 healthy donors. We performed gene expression profile analysis of AtMs stimulated or not by TLR9. Immunoglobulin gene repertoire and antibody reactivity profiles of AtM-expressing IgM antibodies were analysed following single B cell FACS sorting and expression-cloning of monoclonal antibodies. The Tbet Our data strongly suggest a central role for TLR9 activation of AtMs in driving HCV-CV autoimmunity through rheumatoid factor production and type 1 T cell responses. B cells are best known for their capacity to produce antibodies, which often play a deleterious role in the development of autoimmune diseases. During chronic hepatitis C, self-reactive B cells proliferate and can be responsible for autoimmune symptoms (arthritis, purpura, neuropathy, renal disease) and/or lymphoma. Direct-acting antiviral therapy clears the hepatitis C virus and eliminates deleterious B cells.
Sections du résumé
BACKGROUND & AIMS
Hepatitis C virus (HCV) infection contributes to the development of autoimmune disorders such as cryoglobulinaemia vasculitis (CV). However, it remains unclear why only some individuals with HCV develop HCV-associated CV (HCV-CV). HCV-CV is characterized by the expansion of anergic CD19
METHODS
The phenotype and function of peripheral AtMs were studied by multicolour flow cytometry and co-culture assays with effector T cells and regulatory T cells in 20 patients with HCV-CV, 10 chronicallyHCV-infected patients without CV and 8 healthy donors. We performed gene expression profile analysis of AtMs stimulated or not by TLR9. Immunoglobulin gene repertoire and antibody reactivity profiles of AtM-expressing IgM antibodies were analysed following single B cell FACS sorting and expression-cloning of monoclonal antibodies.
RESULTS
The Tbet
CONCLUSION
Our data strongly suggest a central role for TLR9 activation of AtMs in driving HCV-CV autoimmunity through rheumatoid factor production and type 1 T cell responses.
LAY SUMMARY
B cells are best known for their capacity to produce antibodies, which often play a deleterious role in the development of autoimmune diseases. During chronic hepatitis C, self-reactive B cells proliferate and can be responsible for autoimmune symptoms (arthritis, purpura, neuropathy, renal disease) and/or lymphoma. Direct-acting antiviral therapy clears the hepatitis C virus and eliminates deleterious B cells.
Identifiants
pubmed: 31279905
pii: S0168-8278(19)30401-5
doi: 10.1016/j.jhep.2019.06.029
pii:
doi:
Substances chimiques
Autoantibodies
0
Immunoglobulin M
0
Receptors, Complement 3d
0
TLR9 protein, human
0
Toll-Like Receptor 9
0
Tumor Necrosis Factor Receptor Superfamily, Member 7
0
Rheumatoid Factor
9009-79-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
908-919Informations de copyright
Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.