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Identification and analysis of biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis by quantitative proteomics

Research Project

Project/Area Number 17K16209
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionEhime University

Principal Investigator

Ishizaki Jun  愛媛大学, 医学部附属病院, 講師(病院教員) (00620527)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsANCA関連血管炎 / バイオマーカー / ターゲットプロテオミクス / 顕微鏡的多発血管炎 / 多発血管炎性肉芽腫症 / 好酸球性多発血管炎性肉芽腫症 / 臓器障害マーカー / 臨床免疫学
Outline of Final Research Achievements

We identified promising biomarkers of disease activity and organ involvement in AAV with a targeted proteomics approach. Our analysis demonstrated the effectiveness of TIMP-1 as a marker of AAV disease activity. We identified CD93 and Transketolase as novel markers for evaluation of renal involvement and renal outcome in AAV. In skin, stomach and renal involvement in AAV patients, TIMP-1 was expressed in S100-positive mesenchymal cells and CD93 was expressed in CD31-positive vascular endothelial cells. Soluble form of CD93 induced the productions of TNF-α, IL-6 and IL-8 from local macrophages in a concentration dependent manner.

Academic Significance and Societal Importance of the Research Achievements

ANCA関連血管炎(AAV)の活動性マーカーであるANCA値やCRPは必ずしも疾患活動性や臓器障害を反映せず、新規バイオマーカーが望まれている。我々は質量分析を用いた選択的反応モニタリング法により微量タンパク質の高感度な一斉定量解析を行い、AAVの血清プロテオームを大規模解析し、既存マーカーより優れた活動性マーカー(TIMP-1)や新規の腎病変マーカー(CD93、TKT)を同定した。新規マーカーによる客観的な活動性および重症度評価を確立することで、適切な治療決定、治療効果判定や再燃予測が可能となる。マーカータンパク質の発現細胞や機能解析により疾患発症機序の解明や新規治療標的の探索につながる。

Report

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

    (9 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] 血管炎症候群2020

    • Author(s)
      石﨑淳、長谷川均
    • Journal Title

      リウマチ科

      Volume: 63 Pages: 28-36

    • Related Report
      2019 Annual Research Report
  • [Journal Article] ANCA関連血管炎のプロテオミクス2020

    • Author(s)
      武森信暁、石﨑淳、長谷川均
    • Journal Title

      炎症と免疫

      Volume: 28 Pages: 3-8

    • Related Report
      2019 Annual Research Report
  • [Journal Article] ANCA関連血管炎のバイオマーカー2018

    • Author(s)
      石崎淳、長谷川均
    • Journal Title

      リウマチ科

      Volume: 60 Pages: 60-68

    • Related Report
      2018 Research-status Report
  • [Journal Article] ANCA関連血管炎の活動性バイオマーカー2018

    • Author(s)
      長谷川均、石崎淳
    • Journal Title

      日本臨牀 増刊号 血管炎(第2版)

      Volume: 76 Pages: 492-498

    • Related Report
      2018 Research-status Report
  • [Journal Article] Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis2017

    • Author(s)
      Ishizaki Jun, Takemori Ayako, Suemori Koichiro, Matsumoto Takuya, Akita Yoko, Sada Ken-ei, Yuzawa Yukio, Amano Koichi, Takasaki Yoshinari, Harigai Masayoshi, Arimura Yoshihiro, Makino Hirofumi, Yasukawa Masaki, Takemori Nobuaki, Hasegawa Hitoshi
    • Journal Title

      Arthritis Research & Therapy

      Volume: 19 Issue: 1 Pages: 218-218

    • DOI

      10.1186/s13075-017-1429-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ANCA関連血管炎の寛解導入および寛解維持期における疾患活動性マーカーとしての血清TIMP1値の有用性の検討2019

    • Author(s)
      石﨑淳、松本卓也、末盛浩一郎、竹中克斗、長谷川均
    • Organizer
      第63回日本リウマチ学会・学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ANCA関連血管炎における新規マーカーCD93の病態への関与2018

    • Author(s)
      石﨑淳, 松本卓也, 末盛浩一郎, 長谷川均
    • Organizer
      第62回日本リウマチ学会・学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 質量分析を用いた大規模プロテオーム解析によるANCA関連血管炎の新規活動性および臓器障害マーカーの探索2017

    • Author(s)
      石﨑淳、松本卓也、末盛浩一郎、安川正貴、長谷川均
    • Organizer
      第61回日本リウマチ学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Identification of Circulating Biomarkers of Disease Activity and Organ Involvement in ANCA-Associated Vasculitis By Targeted Proteomics2017

    • Author(s)
      Jun Ishizaki, Ayako Takemori, Koichiro Suemori, Takuya Matsumoto, Yoko Akita, Masaki Yasukawa, Nobuaki Takemori and Hitoshi Hasegawa
    • Organizer
      2017 ACR/ARHP Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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