Investigation of pathogenesis and pathophisiology of anti-MDA5-positive dermatomyositis

• Project/Area Number: 25860808
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto University
• Principal Investigator: NAKASHIMA Ran 京都大学, 医学(系)研究科(研究院), 助教 (10599525)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 皮膚筋炎 / 抗MDA5抗体 / 間質性肺炎 / 単球 / マクロファージ / 抗MDA抗体 / HLA

Outline of Final Research Achievements

The purpose was to investigate the pathophisiology of anti-MDA5-positive DM and the pathogenicity of MDA5 or anti-MDA5 antibody.
An autopsy of anti-MDA5-positive DM with rapidly progressive interstitial lung disease(ILD) revealed that a lot of macrophages infiltrated to alveoli in the lesion of ILD. Moreover, IP-10, which stimulate the activation of monocyte and macrophage, was highly expressed in the damaged alveoli and fibrotic change after inflammation. In vitro, it was suggested that anti-MDA5-positive IgG stimulated monocytes producing more IL-6 than normal control(NC) in the coexistence of poly I:C. MDA5 was detected more frequently in anti-MDA5-positive patients than NC and its concentration was also higher in the patients than in HC. Serum MDA5 may react with anti-MDA5 and play some role in the pathophisiology in anti-MDA5-positive DM. HLA DRB1＊13:02-DQB1＊06:04 -DQB1＊06:04 was associated with anti-MDA5-positive dermatomyositis as a genetic background.

Research Products

• [Journal Article] Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease (2016)
  • Author(s): Ran Nakasima, Yuji Hosono, Tsuneyo Mimori
  • Journal Title: Lupus Volume: 未定
  • Peer Reviewed
• [Journal Article] Anti-MDA5 (melanoma differentiation-associated gene 5) antibody and dermatomyositis with rapidly progressive interstitial pneumonia (2013)
  • Author(s): Ran Nakashima, Tsuneyo Mimori
  • Journal Title: Clinical Immunology Volume: 36 Pages: 71-76
  • NAID: 10031171396
• [Journal Article] The prognostic value of HRCT in myositis-associated interstitial lung disease. (2013)
  • Author(s): Tanizawa K, Handa T, Nakashima R, Kubo T, Hosono Y, Aihara K, Ikezoe K, Watanabe K, Taguchi Y, Hatta K, Oga T, Chin K, Nagai S, Mimori T, Mishima M
  • Journal Title: Respiratory Medicine Volume: 107 Pages: 745-52
  • Peer Reviewed
• [Presentation] Risk factors for life prognosis of interstitial lung disease in dermatomyositis patients with anti-MDA 5 antibody (2015)
  • Author(s): Yuji Hosono, Ran Nakashima, Yoshitaka Imura, Naoichiro Yukawa, Hajime Yoshifuji, Koichiro Ohmura and Tsuneyo Mimori
  • Organizer: American college of Rheumatology Annual Meeting 2015
  • Place of Presentation: San Francisco
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] The onset of myositis with myositis-specific autoantibodies (MSAs) are associated with the seasons. (2013)
  • Author(s): Yuji Hosono, Ran Nakashima, Yoshitaka Imura, Naoichiro Yukawa, Hajime Yoshifuji, Motomu Hashimoto, Koichiro Ohmura, Takao Fujii and Tsuneyo Mimori
  • Organizer: EULAR
  • Place of Presentation: Madrid
• [Presentation] 急速進行性間質性肺炎を合併する抗MDA5抗体陽性皮膚筋炎の強力免疫抑制療法による生命予後の改善 (2013)
  • Author(s): 中嶋 蘭、細野 祐司、井村 嘉孝、湯川 尚一郎、吉藤 元、 大村 浩一郎、藤井 隆夫、三森 経世
  • Organizer: 第110回日本内科学会講演会
  • Place of Presentation: 東京
• [Presentation] 多発性筋炎/皮膚筋炎に伴う間質性肺炎の新しい診断と治療アプローチ (2013)
  • Author(s): 中嶋 蘭
  • Organizer: 第23回日本リウマチ学会近畿支部集会
  • Place of Presentation: 大阪
  • Invited