Regulation of autoantibogy glycosylation by follicular helper T cells in rheumatoid arthritis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17879
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: University of Tsukuba
• Principal Investigator: Kurata Izumi 筑波大学, 医学医療系, 非常勤研究員 (80830108)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 関節リウマチ / 自己抗体 / 糖鎖 / 濾胞性ヘルパーT細胞 / OX40

Outline of Final Research Achievements

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic arthritis, and severe infections caused by immunosuppressive therapy remain a problem in its treatment. We aimed to develop an autoantibody-specific therapy that does not require pan-immunosuppression using RA model mice and patient blood. We clarified that in the early stage of arthritis, the number of follicular helper T cells increased in the lymph nodes, and they highly expressed OX40 on their cell surface. Moreover, they could regulate glycosylation of autoantibodies and control their pathogenicity via OX40.

Free Research Field

膠原病リウマチ学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、糖鎖修飾、すなわち自己抗体の「質」を制御するという全く新たなRA治療の可能性が示唆された。糖鎖修飾の変化は自己抗体特異的な現象であり、同治療は汎免疫抑制に依らず自己免疫のみを標的としたものとなり得る。
また、抗体の糖鎖修飾変化は全身性エリテマトーデス等他の自己免疫疾患でも報告されている。本研究で見出されたOX40による制御はそれらに対しても共通している可能性がある。