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

  • Ling Fang
  • Xinmei Kang
  • Zhen Wang
  • Shisi Wang
  • Jingqi Wang
  • Yifan Zhou
  • Chen Chen
  • Xiaobo Sun
  • Yaping Yan
  • Allan G. Kermode
  • Lisheng PengEmail author
  • Wei QiuEmail author
Original Article
  • 77 Downloads

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.

Keywords

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

Notes

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81471218 and 81771300) and the Natural Science Foundation of Guangdong Province, China (2017A030313853). We thank Professors Yiwen Ruan and Yunfeng Shi at Jinan University who supported the electron microscopy experiments.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Ling Fang
    • 1
  • Xinmei Kang
    • 1
  • Zhen Wang
    • 2
    • 3
  • Shisi Wang
    • 1
  • Jingqi Wang
    • 1
  • Yifan Zhou
    • 1
  • Chen Chen
    • 1
  • Xiaobo Sun
    • 1
  • Yaping Yan
    • 3
  • Allan G. Kermode
    • 1
    • 4
  • Lisheng Peng
    • 1
    Email author
  • Wei Qiu
    • 1
    Email author
  1. 1.Department of NeurologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  2. 2.Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
  3. 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 SciencesShaanxi Normal UniversityXi’anChina
  4. 4.Department of Neurology, Centre for Neuromuscular and Neurological Disorders, Queen Elizabeth II Medical Centre, Sir Charles Gairdner HospitalUniversity of Western AustraliaPerthAustralia

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