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Identification of pathomechanism in rapidly progressive interstitial lung disease associated with myositis

Research Project

Project/Area Number 17K09988
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionNippon Medical School

Principal Investigator

Gono Takahisa  日本医科大学, 医学部, 准教授 (00418724)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords間質性肺疾患 / 単球マクロファージ / miRNA / mRNA / 筋炎 / マクロファージ / マイクロアレイ / パスウエイ解析 / miRNA-mRNA統合解析 / 新規バイオマーカー / 検体採取 / 免疫学 / トランスレーショナルリサーチ
Outline of Final Research Achievements

We aimed to identify molecules and pathways involved in activated CD14+ monocyte/macrophage-lineage cells in patients with rapidly progressive interstitial lung disease associated (RP-ILD) with myositis by using an integrated miRNA-mRNA association analysis and identified molecules related to disease pathways and regulator effect network by Ingenuity Pathway Analysis (IPA) system. Twenty-six significant matched pairs of differentially down-regulated miRNA and up-regulated mRNA were by IPA. We identified 6 relevant genes associated with disease pathways. In the regulator effect network analysis by IPA, 5 predicted upstream regulators were clarified. Disease X was identified as the predicted downstream effect involved with those 6 relevant genes. In conclusion, disease X-associated pathways in monocyte/macrophage-lineage cells is involved in the pathophysiology of RP-ILD.

Academic Significance and Societal Importance of the Research Achievements

今回の研究にて、はじめて、疾患の病態に関連している免疫細胞である単球・マクロファージの活性化の仕組みが明らかとなった。そのことで、今後、新しい治療法の開発研究に貢献し得るものと思われる。また、この疾患の治療効果をリアルタイムに判定できる基準が、これまで明確になっていなかったが、本研究で同定した分子を測定することでリアルタイムに治療効果を判定し得る可能性がある。今後、日常診療において新しい治療効果判定の開発とその確立を目指していく。

Report

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

    (5 results)

All 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (3 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Current Understanding and Recent Advances in Myositis-Specific and -Associated Autoantibodies Detected in Patients With Dermatomyositis2020

    • Author(s)
      Takahisa Gono
    • Journal Title

      Expert Rev Cin Immunol

      Volume: 16 Issue: 1 Pages: 79-89

    • DOI

      10.1080/1744666x.2019.1699059

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improved Quantification of a Commercial Enzyme-Linked Immunosorbent Assay Kit for Measuring anti-MDA5 Antibody2019

    • Author(s)
      Takahisa Gono
    • Journal Title

      Mod Rheumatol

      Volume: 29 Issue: 1 Pages: 140-145

    • DOI

      10.1080/14397595.2018.1452179

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Predictive Factors for Mortality in Anti-melanoma-associated Gene 5 Antibody-associated Interstitial Lung Disease2019

    • Author(s)
      Takahisa Gono
    • Organizer
      2019 ACR/ARP Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Risk Stratification for Mortality in Patients with Anti-melanoma Differentiation-associated Gene 5 Antibody-associated Interstitial Lung Disease2019

    • Author(s)
      Takahisa Gono
    • Organizer
      2019 East Asian Group Of Rheumatology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Risk stratification in patients with Anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease treated initially with intensive combination regimen2019

    • Author(s)
      Takahisa Gono
    • Organizer
      Global conference on myositis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-12-27  

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