Study for pathological significance of autoantibodies and establishment of therapy in myositis-associated intractable acute interstitial pneumonia

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293222
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto University
• Principal Investigator: MIMORI Tsuneyo 京都大学, 医学(系)研究科(研究院), 教授 (10157589)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• 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

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.

Free Research Field

医歯薬学