Detection of disease biomarkers in juvenile dermatomyositis using proteomics and assessment of racial differences

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10045
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Karasawa Rie 聖マリアンナ医科大学, 医学研究科, 准教授 (50434410)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 若年性皮膚筋炎 / 抗血管内皮細胞抗体 / プロテオミクス / 国際共同研究

Outline of Final Research Achievements

HSC70 was one of the target autoantigens for anti-endothelial cell antibodies (AECA) identified in children with juvenile dermatomyositis (JDM). The frequency of anti-HSC70 autoantibodies (Abs) in plasma was significantly higher in JDM than in juvenile idiopathic arthritis, Kawasaki disease and healthy individuals. The presence of anti-HSC70 Abs was significantly increased in the presence of myositis autoantibodies. Mean levels of serum AST in JDM children with anti-HSC70 Abs were significantly higher than those without anti-HSC70 Abs. The presence of anti-HSC70 Abs was strongly associated with physician global damage assessment (MDDMAVAS). A history of fever, skin ulcers and the use of wheelchairs and/or devices were associated with anti-HSC70 Abs. Taken together, these findings suggest a correlation between the presence of anti-HSC70 Abs and more severe disease phenotypes. AECA may be involved in the pathophysiology of autoimmune inflammation of blood vessels in JDM.

Free Research Field

リウマチ膠原病学

Academic Significance and Societal Importance of the Research Achievements

若年性皮膚筋炎（JDM）では皮膚や筋肉に加え、他の臓器にも血管炎症状が起こり得ることが報告されているが、今までその炎症の場である血管に焦点を当てている研究はほとんどない。JDMで報告されている自己抗体に関しても同様である。本研究で得られた成果は、血管炎患者に高率に認められる自己抗体である抗血管内皮細胞抗体（AECA）がJDMで検出され、AECAの対応抗原であるHSC70に対する自己抗体の出現が重度の疾患フェノタイプと相関することを示したことである。したがって、AECAがJDMにおける血管壁の炎症や自己免疫の病態生理に関与している可能性が示唆された。