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Exploration of pathogenetic role of citrullinated ITIH4 in rheumatoid arthritis

Research Project

Project/Area Number 18K08403
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Matsumoto Isao  筑波大学, 医学医療系, 准教授 (30343081)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords関節リウマチ / ITIH4 / シトルリン化蛋白 / 好中球
Outline of Final Research Achievements

We found specific disease plasma marker, citrullinated inter-alpha-trypsin inhibitor heavy chain 4 (cit-ITIH4) in plasma in pGIA model and rheumatoid arthritis (RA). Cit-ITIH4 is highly concentrated in synovial fluid than plasma in RA. Recombinant cit-ITIH4 enhanced neutrophil migration and complement activation, suggesting exacerbating role in arthritis.

Academic Significance and Societal Importance of the Research Achievements

関節炎発症時は局所でITIH4濃度及びcit-ITIH4が上昇し、その過程で関節局所に流入する好中球がPAD4発現を上昇させ、局所でのシトルリン化を促すことが判明した(Osada et al. Clin.Exp.Immunol.2021)。これらより、まず血漿cit-ITIT4のELISA同定キットの作成を進めている。また、ITIH4自体の関節炎への関与をより明らかにするために、欠損マウスを用いて研究を進める。関節炎症に特化した制御メカニズムが明らかになり、新たな治療ターゲットの創生が望まれる。

Report

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

    (13 results)

All 2021 2020 2019 2018 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (4 results) (of which Invited: 3 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Citrullinated inter-alpha-trypsin inhibitor heavy chain 4 in arthritic joints and its potential effect in the neutrophil migration.2021

    • Author(s)
      Osada A, Matsumoto I, Mikami N, Ohyama A, Kurata I,Kondo Y, Tsuboi H, Ishigami A, Sano Y, Arai T, Ise N, Sumida T.
    • Journal Title

      Clin Exp Immunol

      Volume: 203 Issue: 3 Pages: 385-399

    • DOI

      10.1111/cei.13556

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Splice variant of STEAP4 localizes in the nucleus, making it a possible transcriptional regulator of IL-6 production.2019

    • Author(s)
      Ebe H, *Matsumoto I, Osada A, Kurata I, Kawaguchi H, Kondo Y, Tsuboi H, Sumida T.
    • Journal Title

      Mod Rheumatol.

      Volume: 29 Pages: 714-716

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peptidyl arginine deiminase inhibition suppresses arthritis via decreased protein citrullination in joints and serum with the downregulation of interlukin-6.2019

    • Author(s)
      Kawaguchi H, *Matsumoto I, Osada A, Kurata I, Ebe H, Tanaka Y, Inoue A, Umeda N, Kondo Y, Tsuboi H, Ishigami A, Sumida T.
    • Journal Title

      Mod Rheumatol.

      Volume: 29 Pages: 964-969

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potential involvement of OX40 in the regulation of autoantibody sialylation in arthritis.2019

    • Author(s)
      Kurata I, *Matsumoto I, Ohyama A, Osada A, Ebe H, Kawaguchi H, Kaneko S, Kondo Y, Tsuboi H, Tomioka A, Kaji H, Sumida T
    • Journal Title

      Ann Rheum Dis.

      Volume: 78 Pages: 1488-1496

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peptidyl arginine deiminase inhibition suppresses arthritis via decreased protein citrullination in joints and serum with the downregulation of interlukin-6.2019

    • Author(s)
      Kawaguchi H, *Matsumoto I, Osada A, Kurata I, Ebe H, Tanaka Y, Inoue A, Umeda N, Kondo Y, Tsuboi H, Ishigami A, Sumida T.
    • Journal Title

      Modern Rheumatology

      Volume: in press

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of novel biomarker as citrullinated inter-alpha-trypsin inhibitor heavy chain 4, specifically increased in sera with experimental and rheumatoid arthritis.2018

    • Author(s)
      Kawaguchi H, *Matsumoto I, Osasda A, Kurata I, Ebe H, Tanaka Y, Inoue A, Umeda N, Kondo Y, Tsuboi H, Shinkai Y, Kumagai Y, Ishigami A, Sumida T.
    • Journal Title

      Arthritis Res Ther

      Volume: 20 Pages: 66-66

    • NAID

      120007128092

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Inter-alpha-trypsin inhibitor heavy chain 4(ITIH4)のシトルリン化機構と補体系への関与の検討2021

    • Author(s)
      長田侑、三上奈津子、大山綾子、藏田泉、近藤裕也、坪井洋人、松本功
    • Organizer
      第65回日本リウマチ学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 関節リウマチにおけるT細胞と抗シトルリン化蛋白抗体のトピックス2019

    • Author(s)
      松本 功
    • Organizer
      第28回日本シェーグレン症候群学会(徳島)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] TNFとその阻害メカニズムupdate-関節リウマチを中心に-2019

    • Author(s)
      松本 功
    • Organizer
      第47回日本臨床免疫学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 関節リウマチの寛解導入・維持療法を再考する2019

    • Author(s)
      松本 功
    • Organizer
      第63回日本リウマチ学会総会・学術集会(京都)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Remarks] 筑波大学 膠原病リウマチアレルギー内科

    • URL

      http://www.md.tsukuba.ac.jp/clinical-med/rheumatology/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 筑波大学医学医療系 膠原病リウマチアレルギー内科

    • URL

      http://www.md.tsukuba.ac.jp/clinical-med/rheumatology/

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 関節リウマチ診断薬2020

    • Inventor(s)
      松本功
    • Industrial Property Rights Holder
      松本功
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report
    • Overseas

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Published: 2018-04-23   Modified: 2022-01-27  

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