Comprehensive analysis of complement and development of therapy against complement in myasthenia gravis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17026
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Chiba University
• Principal Investigator: Ozawa Yukiko 千葉大学, 医学部附属病院, 医員 (50792412)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 重症筋無力症 / 補体 / 補体調整因子

Outline of Final Research Achievements

We investigated changes in serum complements and their regulators in the pathogenesis of myasthenia gravis (MG). Forty-four patients with acetylcholine receptor antibodies-positive MG, as well as 20 patients with noninflammatory neurological disorders were enrolled. Serum complements (C3, C4 and soluble C5b-9) and complement regulators (vitronectin, clusterin and properdin) were extensively analysed by ELISA and the associations with clinical profiles of MG were examined. Serum C3, C4 and clusterin levels were not significantly different between patients with MG and controls. The patients with MG showed higher soluble C5b-9 and vitronectin levels than the controls; moreover, vitronectin levels decreased after treatment. Serum properdin levels were lower in the patients with MG than in the controls, and negatively correlated with the MG activities of daily living score and with the presence of bulbar palsy.

Free Research Field

重症筋無力症

Academic Significance and Societal Importance of the Research Achievements

MG患者では血清のsC5b9およびVitronectinが上昇しており、MGの長期的な予後や治療反応性を反映している可能性が示唆された。また血清のProperdinは低いほどMGの重症度が高い傾向にあり、MG重症度のバイオマーカーとなりうる可能性が示唆された。
現在補体をターゲットとした新規治療薬が次々と開発されており、全身型重症筋無力症において病態と関連した補体・補体調整因子は治療のバイオマーカーとなる可能性がある。