Elucidation of the pathological mechanism of rheumatoid arthritis induced by N-linked glycans in the ACPA variable region

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02962
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: University of Toyama
• Principal Investigator: Ozawa Tatsuhiko 富山大学, 学術研究部医学系, 准教授 (10432105)
• Co-Investigator(Kenkyū-buntansha): 應原 一久 広島大学, 医系科学研究科(歯), 助教 (80550425)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 関節リウマチ / 抗シトルリン化タンパク質抗体 / N-結合型糖鎖 / 破骨細胞

Outline of Final Research Achievements

The variable region of most ACPA IgG molecules in the serum of RA patients carries N-glycan Nevertheless, important issues on the effects of N-glycan on the pathological function of soluble ACPAs in RA are still unclear. The present study showed a monoclonal ACPA, CCP-Ab1, derived from the peripheral blood B-cells of patient with RA promoted osteoclast differentiation, enhanced bone resorption capacity and augmented the exacerbation of experimental arthritis in SKG mice. This insight provides clues to how ACPAs are related to the onset and exacerbation of RA. The inhibition of osteoclast-induced signalling by N-glycans is expected to lead to the development ofnew therapeutic agents for RA.

Free Research Field

免疫学、抗体工学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

ACPA-IgG可変領域のN-結合型糖鎖の新しい意義として、リウマチ学における新たな研究領域の形成に繋がることが期待される。さらに、RAの病因とAPCAによる病態メカニズムの関係を研究する上で重要な結果の一つになり、関連する基礎・臨床医学の発展に寄与することが期待される。また、 ACPAにより破骨細胞への分化を促進するシグナル伝達を対象としたRAの新たな予防や診断、治療の研究への発展に繋がることが期待される。