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

【Author】

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;Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University;Department of Neurology, Xuanwu Hospital, Capital Medical University;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;Department of Neurology, Centre for Neuromuscular and Neurological Disorders, Queen Elizabeth II Medical Centre,Sir Charles Gairdner Hospital, University of Western Australia;

【Institution】

Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University;Department of Neurology, Xuanwu Hospital, Capital Medical University;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;Department of Neurology, Centre for Neuromuscular and Neurological Disorders, Queen Elizabeth II Medical Centre,Sir Charles Gairdner Hospital, University of Western Australia;

【Abstract】

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.

【Keywords】

Neuromyelitis optica spectrum disorder;;Aquaporin-4 immunoglobulin G;;Myelin oligodendrocyte glycoprotein immunoglobulin G;;Complement-dependent cytotoxicity;;Transmission electron microscopy

References

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Total: 21 articles

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