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

Research Project

Project/Area Number 17K09981
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionFukushima 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
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自己炎症 / IL-Iβ / インフラソーム / 成人発症スチル病 / 自己炎症インフラマソーム カスパーゼ1 IL-1 / インフラマソーム / カスパーゼ1 / IL-1 / 内科
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.

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。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results)

  • [Journal Article] Elevated serum levels of checkpoint molecules in patients with adult Still’s disease2020

    • Author(s)
      Fujita Yuya、Asano Tomoyuki、Matsumoto Haruki、Matsuoka Naoki、Temmoku Jumpei、Sato Shuzo、Furuya Makiko Yashiro、Suzuki Eiji、Watanabe Hiroshi、Koga Tomohiro、Kawakami Atsushi、Migita Kiyoshi
    • Journal Title

      Arthritis Research & Therapy

      Volume: 22 Issue: 1 Pages: 22-20

    • DOI

      10.1186/s13075-020-02263-3

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Uric acid-mediated inflammasome activation in IL-6 primed innate immune cells is regulated by baricitinib.2020

    • Author(s)
      Temmoku J, Fujita Y, Matsuoka N, Urano T, Furuya MY, Asano T, Sato S, Matsumoto H, Watanabe H, Kozuru H, Yatsuhashi H, Kawakami A, Migita K.
    • Journal Title

      Mod Rheumatol.

      Volume: 30 Issue: 1 Pages: 1-6

    • DOI

      10.1080/14397595.2020.1740410

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydroxychloroquine inhibits IL-1β production from amyloid-stimulated human neutrophils.2019

    • Author(s)
      Fujita Y, Matsuoka N, Temmoku J, Furuya MY, Asano T, Sato S, Kobayashi H, Watanabe H, Suzuki E, Urano T, Kozuru H, Yatsuhashi H, Koga T, Kawakami A, Migita K.
    • Journal Title

      Arthritis Res Ther.

      Volume: 21(1) Issue: 1 Pages: 250-250

    • DOI

      10.1186/s13075-019-2040-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum amyloid A1 (SAA1) gene polymorphisms in Japanese patients with adult-onset Still's disease.2018

    • Author(s)
      Yashiro M, Furukawa H, Asano T, Sato S, Kobayashi H, Watanabe H, Suzuki E, Nakamura T, Koga T, Shimizu T, Umeda M, Nonaka F, Ueki Y, Eguchi K, Kawakami A, Migita K.
    • Journal Title

      Medicine (Baltimore)

      Volume: 97(49) Issue: 49 Pages: e13394-e13394

    • DOI

      10.1097/md.0000000000013394

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-204-3p inhibits lipopolysaccharide-induced cytokines in familial Mediterranean fever via the phosphoinositide 3-kinase γ pathway2017

    • Author(s)
      Koga Tomohiro,Migita Kiyoshi,Sato Tomohito,Sato Shuntaro,Umeda Masataka,Nonaka Fumiaki,Fukui Shoichi,Kawashiri Shin-ya,Iwamoto Naoki,Ichinose Kunihiro,Tamai Mami,Nakamura Hideki,Origuchi Tomoki,Ueki Yukitaka,Masumoto Junya,Agematsu Kazunaga,Yachie Akihiro,Yoshiura Koh-ichiro,Eguchi Katsumi,Kawakami Atsushi
    • Journal Title

      Rheumatology

      Volume: 57 Issue: 4 Pages: 718-726

    • DOI

      10.1093/rheumatology/kex451

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of serum inflammatory cytokine concentrations in familial Mediterranean fever and rheumatoid arthritis patients2017

    • Author(s)
      Koga T、Kawashiri S-y、Migita K、Sato S、Umeda M、Fukui S、Nishino A、Nonaka F、Iwamoto N、Ichinose K、Tamai M、Nakamura H、Origuchi T、Ueki Y、Masumoto J、Agematsu K、Yachie A、Eguchi K、Kawakami A
    • Journal Title

      Scandinavian Journal of Rheumatology

      Volume: - Issue: 4 Pages: 1-3

    • DOI

      10.1080/03009742.2017.1363281

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2017-04-28   Modified: 2022-01-27  

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