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Elucidation of intractable mechanism of rapidly progressive interstitial lung disease using cytokine panel analysis

Research Project

Project/Area Number 16K09529
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNiigata University

Principal Investigator

Takada Toshinori  新潟大学, 医歯学総合病院, 特任教授 (40361919)

Co-Investigator(Kenkyū-buntansha) 坂上 拓郎  熊本大学, 大学院生命科学研究部(医), 教授 (00444159)
森山 寛史  独立行政法人国立病院機構西新潟中央病院(臨床研究部), 統括診療部, 呼吸器内科医師 (60463981)
朝川 勝明  新潟大学, 医歯学総合病院, その他 (60599158)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords皮膚筋炎 / 間質性肺疾患 / 抗MDA-5抗体 / サイトカインパネル / IL-10 / IL-15 / サイトカイン / 抗CADM-140/MDA5抗体 / ポリミキシンB吸着カラム
Outline of Final Research Achievements

We enrolled patients with anti-MDA-5 antibody-positive amyopathic dermatomyositis (ADM) with interstitial lung disease (ILD) treated from 2000 to March 2017 at the Niigata University Medical and Dental Hospital and Uonuma Kikan Hospital. We performed cytokine panel analysis for preserved serum samples of 17 survival patients and 9 ones who died from respiratory failure. Comparison of concentrations of serum cytokines before treatment showed that IL-15 was significantly higher than those dead (p <0.05). Next, we compared changes in cytokines during the treatment period between 11 survival cases and 6 non-survival. The slopes (rates of change) of IL-10 and IL-15 were significantly higher in the non-surviving group than in the other (p <0.01). We conclude that IL-15 and IL-10 may play an essential role in the progression of anti-MDA-5 antibody positive ADM-ILD.

Academic Significance and Societal Importance of the Research Achievements

多発性筋炎-皮膚筋炎は指定難病の一つで、約30~50%に間質性肺疾患(ILD)を合併する。このうち筋症状に乏しい皮膚筋炎(ADM)は、約半数で急速進行性ILDを合併する。ADMにともなうILDはもっぱら本邦にみられる難治性疾患で、比較的若年者に発症し致死率も高い。しかし、未だに有効な治療法は確立されていない。これまで、ADM-ILD症例を対象としてILDの増悪に関する免疫炎症学的変化を網羅的に探索した報告はなかった。本研究で得られた結果は、本疾患の進行にIL-10やIL-15が関わることを示唆するもので、将来的に抗IL-10抗体や抗IL-15抗体治療に道を開くものと期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Role of IL-15 in interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibody2018

    • Author(s)
      Takada Toshinori、Ohashi Kazumasa、Hayashi Masachika、Asakawa Katsuaki、Sakagami Takuro、Kikuchi Toshiaki、Sato Shinji
    • Journal Title

      Respiratory Medicine

      Volume: 141 Pages: 7-13

    • DOI

      10.1016/j.rmed.2018.06.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mycophenolate mofetil as a therapeutic agent for interstitial lung diseases in systemic sclerosis.2018

    • Author(s)
      Ueda T, Sakagami T, Kikuchi T, Takada T
    • Journal Title

      Respiratory Investigation

      Volume: 56 Issue: 1 Pages: 14-20

    • DOI

      10.1016/j.resinv.2017.11.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mycophenolate mofetil for the patients with interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibodies2017

    • Author(s)
      Masachika Hayashia, Toshiaki Kikuchia, and Toshinori Takada
    • Journal Title

      Clinical Rheumatology

      Volume: 36 Issue: 1 Pages: 239-240

    • DOI

      10.1007/s10067-016-3443-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cytokine profiles of amyopathic dermatomyositis with interstitial lung diseases treated with mycophenolate2017

    • Author(s)
      Masachika Hayashi, Ami Aoki, Katsuaki Asakawa, Takuro Sakagami, Toshiaki Kikuchi, and Toshinori Takada
    • Journal Title

      Respirology Case Reports

      Volume: 5 Issue: 4 Pages: 1-4

    • DOI

      10.1002/rcr2.235

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 筋症状に乏しい抗MDA-5抗体陽性皮膚筋炎にともなう間質性肺疾患に対するミコフェノール酸モフェチル治療2018

    • Author(s)
      高田俊範、吉澤和孝、林正周、朝川勝明、坂上拓郎、菊地利明
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗MDA-5抗体陽性皮膚筋炎にともなう間質性肺炎におけるIL-15の役割2018

    • Author(s)
      高田俊範、吉澤和孝、木村陽介、大橋和政、林正周、菊地利明、佐藤慎二
    • Organizer
      第21回間質性肺炎細胞分子病態研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Serum Cytokine Profiles of Patients with Interstitial Lung Diseases in Amyopathic Dermatomyositis with anti-MDA-5 Antibody2018

    • Author(s)
      T Takada, K Yoshizawa, K Asakawa, T Sakagami, T Kikuchi, S Sato
    • Organizer
      ATS2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mycophenolate Mofetil for Japanese Patients with Interstitial Lung Diseases in Amyopathic Dermatomyositis with Anti-MDA-5 Antibody2017

    • Author(s)
      Toshinori Takada, Katuaki Asakawa, Ami Aoki, Masachika Hayashi, Takuro Sakagami, Toshiaki Kikuchi
    • Organizer
      2017米国胸部疾患学会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗CADM-140/MDA5抗体陽性皮膚筋炎に伴う間質性肺疾患患者の血清サイトカインプロファイル2016

    • Author(s)
      高田俊範、青木亜美、朝川勝明、坂上拓郎、森山寛史、菊地利明
    • Organizer
      第19回間質性肺炎細胞分子病態研究会
    • Place of Presentation
      砂防会館別館(東京都千代田区)
    • Year and Date
      2016-08-20
    • Related Report
      2016 Research-status Report
  • [Presentation] Serum Cytokine Profiles of Anti-CADM-140/MDA5 Positive Patients with Amyopathic Dermatomyositis and Rapidly Progressive Interstitial Lung Disease2016

    • Author(s)
      Toshinori Takada, Ami Aoki, Katsuaki Asakawa, Takuro Sakagami, Hiroshi Moriyama, Toshiaki Kikuchi, Shinji Sato
    • Organizer
      ATS 2016
    • Place of Presentation
      米国サンフランシスコ、モスコーンセンター
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗CADM-140/MDA5抗体陽性皮膚筋炎に伴う間質性肺疾患患者の血清サイトカインプロファイル2016

    • Author(s)
      高田俊範、青木亜美、朝川勝明、坂上拓郎、森山寛史、菊地利明
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-04-08
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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