Antigen specific therapy for rheumatoid arthritis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461462
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: The University of Tokyo
• Principal Investigator: Shoda Hirofumi 東京大学, 医学部附属病院, 助教 (20529036)
• Research Collaborator: NAGAFUCHI Yasumo 東京大学, 医学部附属病院, 助教 ; SAKURAI Keiichi 東京大学, 医学部附属病院, 非常勤医員
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 関節リウマチ / T細胞 / BiP / T細胞受容体

Outline of Final Research Achievements

HLA-DRB1 is the most potent genetic risk locus in rheumatoid arthritis (RA). Autoantigens are presented on HLA-DRB1 and activate CD4+ T cells, which contribute to RA pathogenesis. Here, we analyzed T cell receptor (TCR) repertoire by next generaton sequencing (NGS), and demonstrated that a significant correlation between HLA-DRB1 and TCR repertoires.
We identified HLA-DRB1*0405 epitopes derived from autoantigen, BiP. In RA patients, BiP-specific effector T cells were proliferated and BiP-specific regulatory T cells controled thier proliferations. Tolerance to BiP peptides ameliorated mouse model of arthritis. Furthermore, Mycobacterium HSP70-specific T cell responses were increased in RA, and molecular mimicry is speculated on the basis of autoimmunity to BiP. Taken together, we proposed the new therapeutic approach for RA by autoantigen-specific T cell regulation.

Free Research Field

膠原病