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Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus is the strongest genetic risk factor for rheumatoid arthritis, the relationship between HLA class II alleles and lymphocyte activation remains unclear. We perfo...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935954/ https://www.ncbi.nlm.nih.gov/pubmed/27385284 http://dx.doi.org/10.1038/srep29338 |
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author | Nagafuchi, Yasuo Shoda, Hirofumi Sumitomo, Shuji Nakachi, Shinichiro Kato, Rika Tsuchida, Yumi Tsuchiya, Haruka Sakurai, Keiichi Hanata, Norio Tateishi, Shoko Kanda, Hiroko Ishigaki, Kazuyoshi Okada, Yukinori Suzuki, Akari Kochi, Yuta Fujio, Keishi Yamamoto, Kazuhiko |
author_facet | Nagafuchi, Yasuo Shoda, Hirofumi Sumitomo, Shuji Nakachi, Shinichiro Kato, Rika Tsuchida, Yumi Tsuchiya, Haruka Sakurai, Keiichi Hanata, Norio Tateishi, Shoko Kanda, Hiroko Ishigaki, Kazuyoshi Okada, Yukinori Suzuki, Akari Kochi, Yuta Fujio, Keishi Yamamoto, Kazuhiko |
author_sort | Nagafuchi, Yasuo |
collection | PubMed |
description | Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus is the strongest genetic risk factor for rheumatoid arthritis, the relationship between HLA class II alleles and lymphocyte activation remains unclear. We performed immunophenotyping of peripheral blood mononuclear cells on 91 HLA-DRB1-genotyped RA patients and 110 healthy donors. The frequency of memory CXCR4(+)CD4(+) T cells, and not Th1 and Th17 cells, was significantly associated with disease severity by multiple linear regression analysis. RA patients with one or more susceptible HLA-DR haplotypes (shared epitope: SE) displayed a significantly higher frequency of memory CXCR4(+)CD4(+) T cells. Moreover, the frequency of memory CXCR4(+)CD4(+) T cells significantly correlated with the expression level of HLA-DR on B cells, which was elevated in RA patients with SE. In vitro analysis and transcriptomic pathway analysis suggested that the interaction between HLA-DR and T cell receptors is an important regulator of memory CXCR4(+)CD4(+) T cells. Clinically, a higher frequency of memory CXCR4(+)CD4(+) T cells predicted a better response to CTLA4-Ig. Memory CXCR4(+)CD4(+) T cells may serve as a powerful biomarker for unraveling the linkage between HLA-DRB1 genotype and disease activity in RA. |
format | Online Article Text |
id | pubmed-4935954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49359542016-07-13 Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity Nagafuchi, Yasuo Shoda, Hirofumi Sumitomo, Shuji Nakachi, Shinichiro Kato, Rika Tsuchida, Yumi Tsuchiya, Haruka Sakurai, Keiichi Hanata, Norio Tateishi, Shoko Kanda, Hiroko Ishigaki, Kazuyoshi Okada, Yukinori Suzuki, Akari Kochi, Yuta Fujio, Keishi Yamamoto, Kazuhiko Sci Rep Article Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus is the strongest genetic risk factor for rheumatoid arthritis, the relationship between HLA class II alleles and lymphocyte activation remains unclear. We performed immunophenotyping of peripheral blood mononuclear cells on 91 HLA-DRB1-genotyped RA patients and 110 healthy donors. The frequency of memory CXCR4(+)CD4(+) T cells, and not Th1 and Th17 cells, was significantly associated with disease severity by multiple linear regression analysis. RA patients with one or more susceptible HLA-DR haplotypes (shared epitope: SE) displayed a significantly higher frequency of memory CXCR4(+)CD4(+) T cells. Moreover, the frequency of memory CXCR4(+)CD4(+) T cells significantly correlated with the expression level of HLA-DR on B cells, which was elevated in RA patients with SE. In vitro analysis and transcriptomic pathway analysis suggested that the interaction between HLA-DR and T cell receptors is an important regulator of memory CXCR4(+)CD4(+) T cells. Clinically, a higher frequency of memory CXCR4(+)CD4(+) T cells predicted a better response to CTLA4-Ig. Memory CXCR4(+)CD4(+) T cells may serve as a powerful biomarker for unraveling the linkage between HLA-DRB1 genotype and disease activity in RA. Nature Publishing Group 2016-07-07 /pmc/articles/PMC4935954/ /pubmed/27385284 http://dx.doi.org/10.1038/srep29338 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Nagafuchi, Yasuo Shoda, Hirofumi Sumitomo, Shuji Nakachi, Shinichiro Kato, Rika Tsuchida, Yumi Tsuchiya, Haruka Sakurai, Keiichi Hanata, Norio Tateishi, Shoko Kanda, Hiroko Ishigaki, Kazuyoshi Okada, Yukinori Suzuki, Akari Kochi, Yuta Fujio, Keishi Yamamoto, Kazuhiko Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity |
title | Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity |
title_full | Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity |
title_fullStr | Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity |
title_full_unstemmed | Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity |
title_short | Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity |
title_sort | immunophenotyping of rheumatoid arthritis reveals a linkage between hla-drb1 genotype, cxcr4 expression on memory cd4(+) t cells, and disease activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935954/ https://www.ncbi.nlm.nih.gov/pubmed/27385284 http://dx.doi.org/10.1038/srep29338 |
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