• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Autoantibodies in dermatomyositis-associated interstitial lung disease and establishment of treatment for improved life prognosis

Research Project

Project/Area Number 16H05341
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionKyoto University

Principal Investigator

MImori Tsuneyo  京都大学, 医学研究科, 教授 (10157589)

Co-Investigator(Renkei-kenkyūsha) OMURA Koichiro  京都大学, 大学院医学研究科, 准教授 (40432372)
YOSHIFUJI Hajime  京都大学, 大学院医学研究科, 助教 (20422975)
IMURA Yoshitaka  京都大学, 大学院医学研究科, 助教 (60456895)
NAKASHIMA Ran  京都大学, 大学院医学研究科, 助教 (10599525)
MURAKAMI Kousaku  京都大学, 大学院医学研究科, 助教 (70599927)
Research Collaborator HOSONO Yuji  
TSUJI Hideki  
YAGITA Nasato  
HATTA Kazuhiro  
NOJIMA Takaki  
KATAYAMA Masaki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
KeywordsMDA5 / IFIH1 / SFPQ / 自己抗体 / 間質性肺炎 / 皮膚筋炎 / 免疫抑制療法 / 血漿交換療法 / DDB1 / 無筋症性皮膚筋炎 / 間質性肺病変
Outline of Final Research Achievements

Anti-MDA5 antibody is a specific marker for intractable dermatomyositis (DM) with interstitial lung disease (ILD). We found a novel antibody in patients with anti-MDA5 and identified the target antigen as SFPQ.
To improve the life prognosis of anti-MDA5-positive patients, we conducted a multicenter prospective study to confirm efficacy and safety of the combined immunosuppressive drugs containing high dose glucocorticoid, oral tacrolimus and intravenous cyclophosphamide. Finally, 29 patients with anti-MDA5-positive ILD-DM/CDAM were registered, and the 6 month survival rate as the primary endpoint was 89%, which was significantly higher than that of historical control (33%). Moreover, we found that plasmapheresis was effective for immunosuppressive drug-resistant cases.
Thus, we demonstrate the efficacy of combined immunosuppressive drugs and plasmapheresis against intractable anti-MDA5-positive ILD-DM/CDAM.

Academic Significance and Societal Importance of the Research Achievements

抗MDA5抗体は難治性で死亡率の高い急速進行性間質性肺病変(ILD)を合併する皮膚筋炎(DM)と無筋症性皮膚筋炎(CADM)に特異的に検出される自己抗体である。我々は同疾患の生命予後改善を目的とする多施設共同前向き臨床研究を遂行し、ステロイド大量、タクロリムス、シクロホスファミド間歇静注療法の同時併用療法が有効であることを証明した。さらに、同療法に抵抗性を示す症例に血漿交換療法を併用することでさらなる生命予後の改善を確認した。これらの成績より、有効な治療法が確立されていなかった膠原病の難治性病態の一つであるILD合併DM/CADMのスタンダードな治療法を確立できたものと考える。

Report

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

    (34 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (16 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 16 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 9 results,  Invited: 10 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Seoul National University(韓国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Novel susceptibility alleles in HLA region for myositis and myositis specific autoantibodies in Korean patients. .2019

    • Author(s)
      Kang EH, Go DJ, Mimori T, Lee SJ, Kwon HM, Park JW, Park MH, Song EY, Ha YJ, Lee EY, Lee YJ, Lee EB, Song YW
    • Journal Title

      Semin Arthritis Rheum [Epub ahead of print]

      Volume: 印刷中 Issue: 2 Pages: 283-287

    • DOI

      10.1016/j.semarthrit.2019.03.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease2019

    • Author(s)
      Nakatsuka Yoshinari, Handa Tomohiro, Nakashima Ran, et al.
    • Journal Title

      Rheumatology

      Volume: NA Issue: 8 Pages: 1465-1473

    • DOI

      10.1093/rheumatology/kez065

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of Glucocorticoids and Calcineurin Inhibitors for Anti-aminoacyl-tRNA Synthetase Antibody?positive Polymyositis/dermatomyositis?associated Interstitial Lung Disease: A Propensity Score?matched Analysis2019

    • Author(s)
      Hozumi Hironao、Fujisawa Tomoyuki、Nakashima Ran、Yasui Hideki、Suzuki Yuzo、Kono Masato、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Inui Naoki、Nakamura Yutaro、Mimori Tsuneyo、Suda Takafumi
    • Journal Title

      The Journal of Rheumatology

      Volume: 印刷中 Issue: 5 Pages: 509-517

    • DOI

      10.3899/jrheum.180778

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment consensus for management of polymyositis and dermatomyositis among rheumatologists, neurologists and dermatologists2018

    • Author(s)
      Kohsaka Hitoshi、Mimori Tsuneyo、Kanda Takashi、Shimizu Jun、Sunada Yoshihide、Fujimoto Manabu、Kawaguchi Yasushi、Jinnin Masatoshi、Muro Yoshinao、Ishihara Shoichiro、Tomimitsu Hiroyuki、Ohta Akiko、Sumida Takayuki
    • Journal Title

      Modern Rheumatology

      Volume: 29 Issue: 1 Pages: 1-19

    • DOI

      10.1080/14397595.2018.1521185

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recurrence of anti-MDA5 antibody-positive clinically amyopathic dermatomyositis after long-term remission: A case report.2018

    • Author(s)
      Endo Y, Koga T, Ishida M, Fujita Y, Tsuji S, Takatani A, Shimizu T, Sumiyoshi R, Igawa T, Umeda M, Fukui S, Nishino A, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Kuwana M, Hosono Y, Mimori T, Kawakami A
    • Journal Title

      Medicine (Baltimore)

      Volume: 97(26) Issue: 26 Pages: e11024-e11024

    • DOI

      10.1097/md.0000000000011024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Splicing variant ofWDFY4augments MDA5 signalling and the risk of clinically amyopathic dermatomyositis2018

    • Author(s)
      Kochi Yuta et al.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 77 Issue: 4 Pages: 602-611

    • DOI

      10.1136/annrheumdis-2017-212149

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical Utility of YKL-40 in Polymyositis/dermatomyositis-associated Interstitial Lung Disease2017

    • Author(s)
      Hozumi H, Fujisawa T, Enomoto N, Nakashima R, Enomoto Y, Suzuki Y, Kono M, Karayama M, Furuhashi K, Murakami A, Inui N, Nakamura Y, Mimori T, Suda T
    • Journal Title

      J Rheumatol

      Volume: 44 Issue: 9 Pages: 1394-1401

    • DOI

      10.3899/jrheum.170373

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.2017

    • Author(s)
      Tanizawa K, Handa T, Nakashima R, Kubo T, Hosono Y, Watanabe K, Aihara K, Ikezoe K, Sokai A, Nakatsuka Y, Taguchi Y, Hatta K, Noma S, Kobashi Y, Yoshizawa A, Oga T, Hirai T, Chin K, Nagai S, Izumi T, Mimori T, Mishima M
    • Journal Title

      Respir Med.

      Volume: 127 Pages: 57-64

    • DOI

      10.1016/j.rmed.2017.04.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictive factors for long-term outcome in polymyositis/dermatomyositis-associated interstitial lung diseases.2017

    • Author(s)
      Fujisawa T, Hozumi H, Kono M, Enomoto N, Nakamura Y, Inui N, Nakashima R, Imura Y, Mimori T, Suda T.
    • Journal Title

      Respiratory Investigation

      Volume: 55 Issue: 2 Pages: 130-137

    • DOI

      10.1016/j.resinv.2016.09.006

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Splicing factor proline/glutamine-rich is a novel autoantigen of dermatomyositis and associated with anti-melanoma differentiation-associated gene 5 antibody.2017

    • Author(s)
      Hosono Y, Nakashima R, Serada S, Murakami K, Imura Y, Yoshifuji H, Ohmura K, Naka T, Mimori T
    • Journal Title

      J Autoimmun.

      Volume: 77 Pages: 116-122

    • DOI

      10.1016/j.jaut.2016.11.006

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease2017

    • Author(s)
      Enomoto Y, Suzuki Y, Hozumi H, Mori K, Kono M, Karayama M, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suzuki D, Ogawa N, Nakashima R, Mimori T, Iwashita T, Suda T
    • Journal Title

      Arthritis Res Ther

      Volume: 19 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s13075-016-1214-8

    • NAID

      120005973333

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Association of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease.2017

    • Author(s)
      Yoshida N, Okamoto M, Kaieda S, Fujimoto K, Ebata T, Tajiri M, Nakamura M, Tominaga M, Wakasugi D, Kawayama T, Kuwana M, Mimori T, Ida H, Hoshino T
    • Journal Title

      Respir Investig.

      Volume: 55(1) Issue: 1 Pages: 24-32

    • DOI

      10.1016/j.resinv.2016.08.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enzyme-linked immunosorbent assays for detection of anti-transcriptional intermediary factor-1 gamma and anti-Mi-2 autoantibodies in dermatomyositis.2016

    • Author(s)
      Fujimoto M, Murakami A, Kurei S, Okiyama N, Kawakami A, Mishima M, Sato S, Seishima M, Suda T, Mimori T, Takehara K, Kuwana M
    • Journal Title

      J Dermatol Sci.

      Volume: 84(3) Issue: 3 Pages: 272-281

    • DOI

      10.1016/j.jdermsci.2016.09.013

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive assessment of myositis-specific autoantibodies in polymyositis/ dermatomyositis- associated interstitial lung disease.2016

    • Author(s)
      Hozumi H, Fujisawa T, Nakashima R, Johkoh T, Sumikawa H, Murakami A, Enomoto N, Inui N, Nakamura Y, Hosono Y, Imura Y, Mimori T, Suda T
    • Journal Title

      Respir Med.

      Volume: 121 Pages: 91-99

    • DOI

      10.1016/j.rmed.2016.10.019

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease.2016

    • Author(s)
      Nakashima R, Hosono Y, Mimori T
    • Journal Title

      Lupus

      Volume: 25(8) Issue: 8 Pages: 925-933

    • DOI

      10.1177/0961203316651748

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clinical Utility of an Enzyme-Linked Immunosorbent Assay for Detecting Anti-Melanoma Differentiation-Associated Gene 5 Autoantibodies.2016

    • Author(s)
      Sato S, Murakami A, Kuwajima A, Takehara K, Mimori T, Kawakami A, Mishima M, Suda T, Seishima M, Fujimoto M, Kuwana M
    • Journal Title

      PLoS One.

      Volume: 11(4) Issue: 4 Pages: e0154285-e0154285

    • DOI

      10.1371/journal.pone.0154285

    • NAID

      120005997767

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 抗MDA5交替妖精間質性肺炎合併皮膚筋炎における血漿交換の有用性と治療適応の検討(ポスター発表).2019

    • Author(s)
      白柏魅怜、中嶋蘭、三森経世、他:
    • Organizer
      第116回日本内科学会講演会(名古屋)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Efficacy and Safety of Combined Immunosuppressive Therapy with High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Disease Accompanied by Anti-MDA5-Positive Dermatomyositis -A Multicenter Prospective Study (Oral, Plenary Session).2018

    • Author(s)
      Tsuji H, Nakashima R, Mimori T, et al:
    • Organizer
      American College of Rheumatology 2018 (Chicago, USA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical significance of myositis-specific autoantibodies in inflammatory myopathy (Special Lecture).2018

    • Author(s)
      Mimori T
    • Organizer
      2018 HUHRD International Symposium on Inflammatory Myositis (Seoul, Korea)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Clinical significance of autoantibodies in autoimmune myositis associated with interstitial lung disease and malignancy.2018

    • Author(s)
      Mimori T
    • Organizer
      11th International Congress on Autoimmunity (Lisbon, Portugal)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 膠原病の診断と治療の進歩(招請講演).2018

    • Author(s)
      三森経世
    • Organizer
      第115回日本内科学会講演会(京都)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 膠原病の診断と治療の進歩(招請講演)2018

    • Author(s)
      三森経世
    • Organizer
      第115回日本内科学会(京都)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Clinical significance of autoantibodies in myositis with interstitial lung disease2017

    • Author(s)
      Mimori T
    • Organizer
      LUPUS2017/ Asian Congress on Autoimmunity
    • Place of Presentation
      Melbourne
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Splicing factor proline/glutamine-rich (SFPQ) is a novel autoantigen associated with anti-MDA5 antibody in dermatomyositis and clinically amyopathic dermatomyositis2017

    • Author(s)
      Hosono Y, Nakashima R, Mimori T
    • Organizer
      LUPUS2017/ Asian Congress on Autoimmunity
    • Place of Presentation
      Melbourne
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自己抗体の探索と臨床応用への道(会長講演)2017

    • Author(s)
      三森経世
    • Organizer
      第61回日本リウマチ学会(福岡)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Clinically relevant autoantibodies in myositis with interstitial lung disease and cancer-associated myositis (Invited lecture)2017

    • Author(s)
      Mimori T
    • Organizer
      American College of Rheumatology 2017 (San Diego, USA)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多発性筋炎・皮膚筋炎の 自己抗体と臨床病型(特別講演)2017

    • Author(s)
      三森経世
    • Organizer
      第27回日本小児リウマチ学会(京都)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Splicing Factor Proline/Glutamine-Rich Is a Novel Autoantigen of Dermatomyositis and Associated with Anti-Melanoma Differentiation-Associated Gene 5 Antibody.2016

    • Author(s)
      Yuji Hosono, Ran Nakashima, Kosaku Murakami, Yoshitaka Imura, Satoshi Serada, Minoru Fujimoto, Hajime Yoshifuji, Koichiro Ohmura, Tetsuji Naka and Tsuneyo Mimori.
    • Organizer
      American College of Rheumatology2016/9/28
    • Place of Presentation
      Washington, DC
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多発性筋炎・皮膚筋炎の臨床病型と自己抗体2016

    • Author(s)
      三森 経世
    • Organizer
      日本リウマチ学会総会・学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Clinical significance and new detection systems of myositis-specific autoantibodies2016

    • Author(s)
      Mimori T, Sato S, Kuwana M, Fujimoto M
    • Organizer
      International Congress on Autoimmunity
    • Place of Presentation
      Leipzig
    • Year and Date
      2016-04-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Predictive factors of poor prognosis and utility of plasmaexchange in anti-MDA5(+)dermatomyositis with interstitial lung disease under immunosuppressive therapy.2016

    • Author(s)
      Mirei Shirakashi, Ran Nakashima, Yuji Hosono, Kosaku Murakami, Motomu Hashimoto, Naoichiro Yukawa, Yoshitaka Imura, Hajime Yoshifuji, Masao Tanaka, Koichiro Ohmura, Tsuneyo Mimori
    • Organizer
      The 13th International Workshop on Autoantibodies and Autoimmunity
    • Place of Presentation
      Kyoto
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 筋疾患の診断のためのバイオマーカー2018

    • Inventor(s)
      三森経世、細野祐司、中嶋蘭
    • Industrial Property Rights Holder
      三森経世、細野祐司、中嶋蘭
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 筋疾患の診断のためのバイオマーカー2017

    • Inventor(s)
      三森経世、細野祐司、笹井蘭
    • Industrial Property Rights Holder
      三森経世、細野祐司、笹井蘭
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-233758
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi