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 Peng, Wei Qiu

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalNeuroscience Bulletin
DOIs
Publication statusE-pub ahead of print - 30 Apr 2019

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Myelin-Oligodendrocyte Glycoprotein
Immunoglobulin G
Neuromyelitis Optica
Astrocytes
Cell Death
Aquaporin 4

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Fang, Ling ; Kang, Xinmei ; Wang, Zhen ; Wang, Shisi ; Wang, Jingqi ; Zhou, Yifan ; Chen, Chen ; Sun, Xiaobo ; Yan, Yaping ; Kermode, Allan G. ; Peng, Lisheng ; Qiu, Wei. / Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG. In: Neuroscience Bulletin. 2019.
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title = "Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG",
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 = "Aquaporin-4 immunoglobulin G, Complement-dependent cytotoxicity, Myelin oligodendrocyte glycoprotein immunoglobulin G, Neuromyelitis optica spectrum disorder, Transmission electron microscopy",
author = "Ling Fang and Xinmei Kang and Zhen Wang and Shisi Wang and Jingqi Wang and Yifan Zhou and Chen Chen and Xiaobo Sun and Yaping Yan and Kermode, {Allan G.} and Lisheng Peng and Wei Qiu",
year = "2019",
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Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG. / Fang, Ling; Kang, Xinmei; Wang, Zhen; Wang, Shisi; Wang, Jingqi; Zhou, Yifan; Chen, Chen; Sun, Xiaobo; Yan, Yaping; Kermode, Allan G.; Peng, Lisheng; Qiu, Wei.

In: Neuroscience Bulletin, 30.04.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG

AU - Fang, Ling

AU - Kang, Xinmei

AU - Wang, Zhen

AU - Wang, Shisi

AU - Wang, Jingqi

AU - Zhou, Yifan

AU - Chen, Chen

AU - Sun, Xiaobo

AU - Yan, Yaping

AU - Kermode, Allan G.

AU - Peng, Lisheng

AU - Qiu, Wei

PY - 2019/4/30

Y1 - 2019/4/30

N2 - 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.

AB - 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.

KW - Aquaporin-4 immunoglobulin G

KW - Complement-dependent cytotoxicity

KW - Myelin oligodendrocyte glycoprotein immunoglobulin G

KW - Neuromyelitis optica spectrum disorder

KW - Transmission electron microscopy

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M3 - Article

JO - Neuroscience Bulletin

JF - Neuroscience Bulletin

SN - 1673-7067

ER -