Elucidation of the pathogenic mechanism and treatment strategy for autoimmune GFAP astrocytopathy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Gifu University
• Principal Investigator: Kimura Akio 岐阜大学, 大学院医学系研究科, 准教授 (00362161)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 自己免疫性脳炎 / GFAP / 髄膜脳炎 / 髄膜脳脊髄炎 / 自己抗体 / 免疫療法 / 抗神経抗体

Outline of Final Research Achievements

We identified 298 patients with autoimmune GFAP astrocytopathy (GFAP-A) and clarified their clinical features. There were more men than women, patients initially presented with fever and headache. The neurological findings during the clinical course were diverse and included consciousness disturbance, urinary disturbance, cognitive dysfunction, movement disorders, and papilledema. A linear perivascular radial gadolinium enhancement pattern was observed in about half of patients. Most patients responded to corticosteroid therapies and the prognosis is relatively good. Some patients were refractory to immunotherapies. The neuropathological findings of 11 patients revealed the infiltrations of CD3 positive T cells mainly perivascular lesions accompanied with CD20 positive B cells and macrophages, and presence of reactive astrocytes. The increased CSF levels of inflammatory cytokines and chemokines including CXCL10 could be observed, and might be associated with GFAP-A pathogenesis.

Free Research Field

脳神経内科学

Academic Significance and Societal Importance of the Research Achievements

GFAP抗体の測定系を確立し、自己免疫性GFAPアストロサイトパチーの可能性を疑う上で重要な臨床的特徴を明らかしたことにより、多くの患者の診断が可能となり、ステロイド治療を主体とする免疫療法を介した患者の予後の改善につなげた。一方、一部に存在する難治例に関し、その特徴と治療法の確立が今後の課題として明らかとなった。本研究で得られた病理所見は、本疾患のT細胞を主体とする病態機序を示唆するものであり、既報に一致した。granzymeやperforinを発現したCD8陽性T細胞がアストロサイトの近傍に確認されており、主に抗原特異的T細胞によるアストロサイトの障害が存在する可能性が推測された。