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

2015 Fiscal Year Final Research Report

• 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
• Keywords: 皮膚筋炎 / 抗MDA5抗体 / 間質性肺炎 / 単球 / マクロファージ

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.

Free Research Field

免疫・リウマチ・膠原病