Identification and establishment of novel autoantibody in myelitis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Osaka University
• Principal Investigator: Okuno Tatsusada 大阪大学, 医学系研究科, 助教 (00464248)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 慢性脊髄炎 / 視神経脊髄炎 / アクアポリン４抗体 / 自己抗体

Outline of Final Research Achievements

We established anti-AQP4 recombinant autoantibodies (Ab) from plasmablasts in NMOSD patient’s CSF. Human astrocytes treated with anti-AQP4 Ab produced a significant amount of CCL2 and contributed to the efficient recruitment of monocytes. Moreover, mitochondrial DNA (mtDNA)was released from astrocytes treated with anti-AQP4 Ab. MtDNA further enhanced CCL2 production by monocytes, and it was demonstrated that mtDNA concentration correlated with the efficiency of monocyte recruitment in the CSF of NMOSD patients. These observations highlight that mtDNA which was released from astrocytes damaged by anti-AQP4 Ab has a central role in establishing the inflammatory loop of monocyte recruitment and activation via an innate immunity pathway.
Regarding myelitis　with unknown etiology, we tried to search for antigens We are currently selecting candidate antigens by establishing a cell base and assay.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

アクアポリン４抗体はこれまで免疫吸着カラムから精製して使用していたが、量が限られていた。本研究では国内で初めてリコンビナントアクアポリン４抗体作成に成功しており今後安定的な動物モデル作成が可能になる。またNMOの疼痛は非常に強く、就業や家庭生活の妨げとなり、大きな社会的損失を来しているが、その治療法に結び付くと考えられる。