Establishment of diagnosis and prognostic factors in cerebrospinal fluid based on the condition of inflammatory central nervous disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19504
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: Nishiyama Shuhei 東北大学, 大学病院, 助教 (60636017)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 視神経脊髄炎 / バイオマーカー / アストロサイト / 脳脊髄液

Outline of Final Research Achievements

Inflammatory central nervous system (CNS) diseases such as multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD) have occasionally difficulty in diagnosis and prognosis. In NMOSD, Aquaporin-4 (AQP4) autoimmune-mediated astrocyte functional change by pseudopodal movement disorder has been clarified recently. We measured pseudopodium-related and cell destruction related proteins in cerebrospinal fluid (CSF) based on the pathological condition of inflammatory CNS disease, and examined whether it could be diagnostic and prognostic biomarkers. CSF samples of various inflammatory CNS diseases were analyzed, and CRMP5 and ARPC4 in CSF were significantly elevated in NMOSD with AQP4-IgG, reflecting astrocyte foot process damages. Especially in the group with CSF-CRMP5 elevation, the prognosis is relatively good. It is considered to be one of the good prognostic factors in NMOSD. A therapeutic strategy targeting the astrocytic foot process can be expected in the future.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

多発性硬化症や視神経脊髄炎といった炎症性中枢神経疾患の多くは原因不明で、時に診断や治療に苦慮する。このうちアクアポリン4抗体陽性視神経脊髄炎の脳脊髄液では、アストロサイト足突起に存在する蛋白が上昇しており、このうち脳脊髄液中CRMP5が上昇している患者さんではより予後が良い結果が出た。今後アストロサイト足突起をターゲットとした治療戦略の開発が期待できる。