Mechanisms for production of reactive oxygen species in chondrocytes and synoviocytes derived from patients with rheumatoid arthritis and their involvement in joint destruction

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11032
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Toho University
• Principal Investigator: NAKAJIMA Arata 東邦大学, 医学部, 准教授 (60583995)
• Co-Investigator(Kenkyū-buntansha): 中川 晃一 東邦大学, 医学部, 教授 (30400823)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 関節リウマチ / 酸化ストレス / 寛解予測 / バイオマーカー / 関節破壊

Outline of Final Research Achievements

To verify whether serum levels of reactive oxygen metabolites (ROM) are predictive of future clinical remission in patients with rheumatoid arthritis (RA) receiving tocilizumab (TCZ) therapy. A total of 46 patients with RA receiving TCZ therapy were enrolled in this study. Patients were divided into remission and non-remission groups based on DAS28 at 52 weeks. Associations between serum levels of ROM, CRP, and MMP-3 at 4 and 12 weeks and the DAS-remission at 52 weeks were investigated.
There were no significant differences in CRP and MMP-3 between DAS-remission and non-remission groups at 12 weeks. However, ROM in DAS-remission group were significantly lower than those in the non-remission group. For ROM, an AUC of the ROC curve was 0.735 and the cut-off value was 305.5 U.Carr (sensitivity: 70.0%, specificity: 72.2%). A multivariate logistic regression analysis revealed that ROM at 12 weeks was associated with DAS-remission at 52 weeks (OR: 6.067, 95% CI: 1.305-28.203).

Free Research Field

リウマチ学

Academic Significance and Societal Importance of the Research Achievements

IL-6受容体抗体のトシリズマブ(TCZ)は関節リウマチ(RA)患者に広く使用されているバイオ製剤である。しかしながら、TCZはCRPなどの急性反応物質の産生を強力に抑制する。このため実臨床ではCRPと臨床症状との乖離が見られることがあり、寛解予測のためのバイオマーカーの開発が望まれている。
本研究の結果、TCZ治療開始後12週における血中酸化ストレスマーカーであるROMが52週のDAS寛解を予測することが明らかとなった。治療効果判定にしばしば用いられるCRP, MMP-3はDAS寛解とは関連がなかったことから、ROMはTCZ治療早期寛解予測のバイオマーカーとして有用と考えられる。