Exploratory research on predictive markers for TNF inhibitor response using single synovial cell analysis of patients with rheumatoid arthritis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16354
• 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: The University of Tokyo
• Principal Investigator: Tsuchiya Haruka 東京大学, 医学部附属病院, 講師 (50868560)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 関節リウマチ / TNF-α阻害剤 / 治療抵抗性 / 滑膜線維芽細胞

Outline of Final Research Achievements

This project was designed to shed light on the mechanism of acquired resistance to TNF- inhibitors by integrating single cell information from the synovial membrane of rheumatoid arthritis (RA) patients and prospectively collected clinical information. The applicants revealed that patients with an abundance of a specific subpopulation of synovial fibroblasts (SFs) showed poor therapeutic response to TNF-α inhibitors administered prospectively. In addition, these subpopulations expressed specific cancer-related molecules and chemokines at higher levels than other SFs subpopulations. The exploration of the induction mechanisms of SFs related to treatment resistance at the inflammatory site is expected to lead to an understanding of part of the intractable pathology of RA.

Free Research Field

自己免疫疾患

Academic Significance and Societal Importance of the Research Achievements

関節リウマチは、遺伝的素因や環境因子を背景に発症する代表的な自己免疫性関節炎である。約10%の患者は既存の抗リウマチ薬の効果が不十分であり、関節破壊が進行する。本課題では、滑膜シングルセル情報と臨床情報の統合的解析を通じて、特定の滑膜線維芽細胞の亜集団がTNF-α阻害剤に対する治療抵抗性に関連することを明らかにした。このことは、難治例に対する新規創薬ターゲット同定に繋がる可能性を内包している。