The role of innate immunology in the patients with early rheumatoid arthritis and resistant-anti rheumatic drugs

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10995
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Yamagata University
• Principal Investigator: Takakubo Yuya 山形大学, 医学部, 准教授 (80431641)
• Co-Investigator(Kenkyū-buntansha): 高木 理彰 山形大学, 医学部, 教授 (40241707) ; 佐々木 幹 山形大学, 医学部, 非常勤講師 (00444034) ; 長沼 靖 山形大学, 医学部, 客員研究員 (10463811) ; 大木 弘治 山形大学, 医学部, 非常勤講師 (20463812)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 関節リウマチ / 薬剤耐性 / 自然免疫 / Toll様受容体 / 制御性免疫

Outline of Final Research Achievements

The aim of this study was to investigate the immuneinflammatory cells, including Toll-like receptors (TLRs)- equipped cells, in synovial tissue and fluid samples from the patients with early and established rheumatoid arthritis (RA) with/without treatment of synthetic disease-modifying antirheumatic drug (sDMARD) including biologics.
T and B cell counts were lower in the biologics than in the csDMARD group (p<0.05). In contrast, the C-reactive protein (CRP) and disease activity score DAS28-CRP did not show clear-cut correlations with the inflammatory grade of the synovitis. Similar numbers of cells immunoreactive for TLR-1 to TLR-9 were found in synovitis in both groups.
Patients clinically responding to biologics might still have the potential of moderate/severe local joint inflammation, composed in particular of and possibly driven by the autoinflammatory TLR+ cells.

Free Research Field

関節リウマチ

Academic Significance and Societal Importance of the Research Achievements

関節リウマチに対する適切な治療介入により，自然免疫，獲得免疫とも抑制され，制御性免疫細胞が増加する傾向がみられたが，Toll様受容体陽性細胞を中心に，自然免疫系反応が残存しやすいことが示唆された。
今後，従来型の疾患修飾性抗リウマチ薬や生物学的製剤，分子標的型合成抗リウマチ薬を用いても症状の寛解が得られない患者では，自然免疫系反応をターゲットとした治療が重要になると結論づけられた。