Single-cell analysis of autoimmune encephalitis of unknown etiology for treatment stratification

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16577
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Osaka University
• Principal Investigator: Ishikura Teruyuki 大阪大学, 大学院医学系研究科, 招へい教員 (80838524)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 自己免疫性脳炎 / 視神経脊髄炎スペクトラム障害 / アクアポリン4抗体 / 神経障害性疼痛

Outline of Final Research Achievements

We collected clinical information, cerebral spinal fluid, serum, and peripheral blood mononuclear cells from autoimmune encephalitis patients. We generated patient-derived aquaporin 4 antibody by Single-cell sorting of cerebral spinal fluid plasmablasts from neuromyelitis optica spectrum disorder (NMOSD) patients. By injecting the antibody directly into the rat spinal cord, we created a NMOSD pain animal model and clarified the pain mechanism focusing on ATP. Currently, we are still screening for anti-neuronal antibodies in cerebral spinal fluid and serum of autoimmune encephalitis patients using rat brain sections, and some samples containing anti-neuronal antibodies have been collected. We hope to create an animal model in the future by generating pathogenic autoantibodies from cerebral spinal fluid cells and peripheral blood mononuclear cells from the autoimmune encephalitis patients.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

NMOSD患者の疼痛を呈する割合は高く、薬剤抵抗性であり、QOLを大きく低下させるため臨床的に大きな問題となっている。今回動物モデルを用いてNMOSD疼痛にATPが重要であることを示し、治療方法に結び付くと考えられる。またシングルセルソーティングによって得られた患者由来自己抗体から動物モデルを作成する手法は、自己免疫性脳炎にも今後適応することができると考えている。