Study on the anti-MOG antibody-related autoimmune optic neuritis

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K11477
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Niigata University
• Principal Investigator: Tanaka Keiko 新潟大学, 脳研究所, 非常勤講師 (30217020)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 急性視神経炎 / 抗MOG抗体 / 抗AQP4抗体 / ヒト型MOG発現マウス / 炎症病態機序

Outline of Final Research Achievements

Autoimmune optic neuritis with anti-AQP4 or anti-MOG antibodies differ in their clinical features, neuropathology, treatment response, and prognosis. We aimed to identify immunological and pathophysiological difference between them using transgenic mice expressing human-type AQP4 or MOG and treatment with each antibody, and to propose proper treatment methods based on each pathogenesis. Since patients’antibodies do not recognize mouse MOG efficiently, we produced human-type MOG (hMMOG) expressing transgenic mice and administred MOG-sensitized lymphocytes intravenously and later anti-MOG IgG from the patients with MOG-antibody-positive optic neuritis patients. In comparison with previously produced human-AQP4 expressing mice treated with AQP4 antibodies, the clinical phenotype did not differ between them, however, inflammatory changes with complement deposition are very weak in hMOG mouse that need different treatment strategies.

Free Research Field

神経免疫学, 脳神経内科学

Academic Significance and Societal Importance of the Research Achievements

急性視神経炎を生じるAQP4抗体陽性NMOSDとMOG抗体関連疾患 (MOGAD) は多発性硬化症とは異なる難治性の自己免疫性疾患である．それぞれの臨床像や経過・治療法が異なると考えられるが，MOGADの病態は不明である．我々は，ヒト型AQP4/MOGを発現する遺伝子改変マウスを作製し，各抗体投与マウスの中枢神経組織変化，免疫的病態を比較検討した．MOGADモデルでは組織炎症変化が軽度で補体の関与も乏しい．AQP4群では組織保護を目指した補体活性抑制を要するが，MOGADでは炎症抑制が主である．病態に基づく治療選択により、患者の療養支援体制や医療経済上の負担が大きく異なることを明らかにした．