Pathogenesis of Chronic Skin Ulcers by anti-HLA Class II/Misfolded Protein Complex Antibodies

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Osaka University
• Principal Investigator: Arase Noriko 大阪大学, 大学院医学系研究科, 助教 (30360481)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 抗Ro52/IgG/HLA-クラスII複合体抗体 / Ro52 / 皮膚筋炎 / 抗MDA5抗体 / 抗合成酵素抗体

Outline of Final Research Achievements

We found that the misfolded protein/HLA class II complex is transported to the cell surface and autoantibodies against the complex are produced in various connective tissue diseases. We have discovered that Ro52 forms a complex with IgG/HLA class II and is transported to the cell surface. This anti-Ro52/IgG/HLA-class II complex antibody was positive in about 90% of patients with anti-MDA5 antibody-positive dermatomyositis which are prone to skin ulceration, and anti-synthetase antibody syndrome sera. Changes in antibody titers of the complex antibodies were associated with changes in disease status, suggesting that this complex may have pathogenic roles.

Free Research Field

皮膚科

Academic Significance and Societal Importance of the Research Achievements

原因不明の慢性皮膚潰瘍は患者のQOLが極めて低く、皮膚科医にとっても治療に難渋する疾患の一つである。私たちは以前原因不明の慢性皮膚潰瘍患者の約３割で抗リン脂質抗体症候群のサブタイプの抗β2GPI/HLA-DR抗体が陽性であることを発見した。今回それらに加えて皮膚潰瘍を作りやすい抗MDA5抗体陽性皮膚筋炎患者で新たに抗Ro52/IgG/HLA-DR抗体が陽性となることを見出した。これらの新たな自己抗体の病原性を明らかにすることは学術的に重要で、これらに関連した治療法を開発することは社会的意義がある。