Autoinflammatory biomarker for the new classification of rheumatic disease and identification of therapeutic target

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Fukushima Medical University
• Principal Investigator: Migita Kiyoshi 福島県立医科大学, 医学部, 教授 (60264214)
• Co-Investigator(Kenkyū-buntansha): 浦野 健 島根大学, 学術研究院医学・看護学系, 教授 (70293701) ; 川上 純 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 自己炎症 / IL-Iβ / インフラソーム / 成人発症スチル病

Outline of Final Research Achievements

Cold inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that respond to cellular stress and has been identified as danger-associated molecular patterns (DAMPs) that trigger the inflammatory response. The aim of this study is to investigate the clinical significance of serum CIRP levels in Adult Still’s disease (AOSD). Serum samples were obtained from 42 patients with active AOSD. Serum levels of CIRP were determined using enzyme-linked immunosorbent assay. Serum CIRP levels were significantly higher in patients with AOSD compared with patients with RA. There was a significant positive correlation between serum CIRP levels and AOSD disease activity score (Pouchet's score). Monosodium urate (MSU) stimulation induced IL-1β secretion from CIRP-primed neutrophils in a dose-dependent manner. These results suggest that CIRP may play a significant role in the pathophysiology of AOSD and could be a potential biomarker for monitoring the disease activity of AOSD.

Free Research Field

臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

ストレス分子であるCIRPがインフラソームの活性化分子であることを世界で初めて証明した。さらに血中のCIRPが自己炎症性疾患であるAOSDで特異的に増加しており、疾患活動性と相関することを明らかにし、AOSDのバイオマーカーであると同時に、AOSDの治療標的になり得ることを明らかにした。