Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG.
10.1007/s12264-019-00375-8
- Author:
Ling FANG
1
;
Xinmei KANG
1
;
Zhen WANG
2
;
Shisi WANG
1
;
Jingqi WANG
1
;
Yifan ZHOU
1
;
Chen CHEN
1
;
Xiaobo SUN
1
;
Yaping YAN
3
;
Allan G KERMODE
1
;
Lisheng PENG
4
;
Wei QIU
5
Author Information
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, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China. penglsh5@mail.sysu.edu.cn.
5. Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China. qiuwei120@vip.163.com.
- Publication Type:Journal Article
- Keywords:
Aquaporin-4 immunoglobulin G;
Complement-dependent cytotoxicity;
Myelin oligodendrocyte glycoprotein immunoglobulin G;
Neuromyelitis optica spectrum disorder;
Transmission electron microscopy
- From:
Neuroscience Bulletin
2019;35(5):853-866
- CountryChina
- Language:English
-
Abstract:
Immunoglobulin G against myelin oligodendrocyte glycoprotein (MOG-IgG) is detectable in neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 IgG (AQP4-IgG), but its pathogenicity remains unclear. In this study, we explored the pathogenic mechanisms of MOG-IgG in vitro and in vivo and compared them with those of AQP4-IgG. MOG-IgG-positive serum induced complement activation and cell death in human embryonic kidney (HEK)-293T cells transfected with human MOG. In C57BL/6 mice and Sprague-Dawley rats, MOG-IgG only caused lesions in the presence of complement. Interestingly, AQP4-IgG induced astroglial damage, while MOG-IgG mainly caused myelin loss. MOG-IgG also induced astrocyte damage in mouse brains in the presence of complement. Importantly, we also observed ultrastructural changes induced by MOG-IgG and AQP4-IgG. These findings suggest that MOG-IgG directly mediates cell death by activating complement in vitro and producing NMOSD-like lesions in vivo. AQP4-IgG directly targets astrocytes, while MOG-IgG mainly damages oligodendrocytes.
