Low CD59 Expression On Astrocyte Contributes To Central Nervous System-restricted Lesion Development In Neuromyelitis Optica Spectrum Disorders

Objective:Neuromyelitis optica spectrum disorder?NMOSD?is mainly an anti-aquaporin 4?AQP4?autoantibody mediated-,central nervous system?CNS?restricted-channelopathy.Patients frequently develop CNS-restricted lesions even though the autoantigen AQP4 in NMOSD is broadly distributed in CNS and peripheral organs.The cause of such tissue-specific immune response remains largely unknown.Methods:CD59 was compared between CNS and periphery organs of human and mice with immunostaining.NMOSD lesions were produced by intracerebral injection of immunoglobulin G isolated from NMO patient serum(IgG_NMO)and human complement in mice with intracerebral pre-injection of CD59 overexpressed or control lentivirus.The complement-dependent cytotoxicity was studied in the cells and tissues from periphery organs with CD59 inactivation or not.Results:CD59 has a lower expression level in astrocytes in CNS but widely expressed and coexisted with AQP4 in periphery organs;CD59 overexpression protected astrocytes and CNS from lesions produced by IgG_NMO and complement in mouse brain;CD59 inactivation in aquaporin 4-expressing cells or tissues of human and mouse periphery organs increased IgG_NMO and complement mediated cytotoxicityConclusions:Our findings suggest that low CD59 expression in astrocytes may contribute to CNS-restricted lesion in NMOSD.Retrieving CD59 expression in astrocytes may serve as a novel therapeutic target in NMOSD.