Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG  

作　　者：Ling Fang Xinmei Kang Zhen Wang Shisi Wang Jingqi Wang Yifan Zhou Chen Chen Xiaobo Sun Yaping Yan Allan G. Kermode Lisheng Peng Wei Qiu 

机构地区：[1]Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China [2]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [3]Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an 710119, China [4]Department of Neurology, Centre for Neuromuscular and Neurological Disorders, Queen Elizabeth II Medical Centre, Sir Charles Gairdner Hospital, University of Western Australia, Perth, WA 6009, Australia

出　　处：《Neuroscience Bulletin》2019年第5期853-866,共14页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (81471218 and 81771300);the Natural Science Foundation of Guangdong Province, China (2017A030313853)

摘　　要：Immunoglobulin G against myelin oligodendrocyte glycoprotein(MOG-Ig G) is detectable in neuromyelitis optica spectrum disorder(NMOSD) without aquaporin-4 Ig G(AQP4-Ig G), but its pathogenicity remains unclear.In this study, we explored the pathogenic mechanisms of MOG-Ig G in vitro and in vivo and compared them with those of AQP4-Ig G. MOG-Ig G-positive serum induced complement activation and cell death in human embryonic kidney(HEK)-293 T cells transfected with human MOG. In C57 BL/6 mice and Sprague-Dawley rats, MOG-Ig G only caused lesions in the presence of complement. Interestingly, AQP4-Ig G induced astroglial damage, while MOGIg G mainly caused myelin loss. MOG-Ig G also induced astrocyte damage in mouse brains in the presence ofcomplement. Importantly, we also observed ultrastructural changes induced by MOG-Ig G and AQP4-Ig G. These findings suggest that MOG-Ig G directly mediates cell death by activating complement in vitro and producing NMOSDlike lesions in vivo. AQP4-Ig G directly targets astrocytes,while MOG-Ig G mainly damages oligodendrocytes.Immunoglobulin G against myelin oligodendrocyte glycoprotein(MOG-Ig G) is detectable in neuromyelitis optica spectrum disorder(NMOSD) without aquaporin-4 Ig G(AQP4-Ig G), but its pathogenicity remains unclear.In this study, we explored the pathogenic mechanisms of MOG-Ig G in vitro and in vivo and compared them with those of AQP4-Ig G. MOG-Ig G-positive serum induced complement activation and cell death in human embryonic kidney(HEK)-293 T cells transfected with human MOG. In C57 BL/6 mice and Sprague-Dawley rats, MOG-Ig G only caused lesions in the presence of complement. Interestingly, AQP4-Ig G induced astroglial damage, while MOGIg G mainly caused myelin loss. MOG-Ig G also induced astrocyte damage in mouse brains in the presence ofcomplement. Importantly, we also observed ultrastructural changes induced by MOG-Ig G and AQP4-Ig G. These findings suggest that MOG-Ig G directly mediates cell death by activating complement in vitro and producing NMOSDlike lesions in vivo. AQP4-Ig G directly targets astrocytes,while MOG-Ig G mainly damages oligodendrocytes.

关 键 词：Neuromyelitis optica spectrum disorder AQUAPORIN-4 IMMUNOGLOBULIN G MYELIN OLIGODENDROCYTE glycoprotein IMMUNOGLOBULIN G Complement-dependent cytotoxicity Transmission electron microscopy 

分 类 号：R[医药卫生]