| Project/Area Number |
25293222
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Kyoto University |
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Principal Investigator |
MIMORI Tsuneyo 京都大学, 医学(系)研究科(研究院), 教授 (10157589)
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| Co-Investigator(Renkei-kenkyūsha) |
FUJII Takao 和歌山大学, 医学部, 教授 (70255462)
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)
YUKAWA Naoichiro 和歌山大学, 医学部, 講師 (90422972)
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)
TERAO Chikashi 京都大学, 大学院医学研究科, 助教 (60610459)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | MDA5 / IFIH1 / 自己抗体 / 皮膚筋炎 / 無筋症性皮膚筋炎 / 間質性肺炎 / 膠原病難治性病態 / 免疫抑制療法 / モデルマウス / 治療 / 難治性病態 |
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| Outline of Final Research Achievements |
Anti-MDA5 autoantibody is specifically detected in patients with clinically amyopathic dermatomyositis accompanied with lethal acute interstitial pneumonia. In order to demonstrate the direct pathogenic role of anti-MDA5, we tried to administrate patient's IgG to SKG mice, but no significant change was found compared with normal IgG. We found a new autoantibody that is associated with anti-MDA5-positive patients, and the target autoantigen was identified as a nuclear molecule involved in DNA repair, mRNA splicing and natural immunity against RNA viral infection. The intensive immunosuppressive therapy (high-dose glucocorticoids, tacrolimus and intravenous cyclophosphamide pulse) appeared to improve a life prognosis of anti-MDA5-positive patients when compared with the historical control of conventional step-up therapy.
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