Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system

Frontiers in Cellular Neuroscience

Cellular Neuroscience

Jo Anne Stratton¹  Maxime Bigotte¹  Adam M. R. Groh¹  Romain Marignier² 

[1] Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada;Forgetting Team—Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR 5292, Claude Bernard Lyon 1 University, Bron, France;Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuroinflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France;

关键词: ependymal cell;    neuroinflammation;    autoantibodies;    B cells;    multiple sclerosis;    neuromyelitis optica;   

DOI  :  10.3389/fncel.2023.1257000

 received in 2023-07-11, accepted in 2023-08-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

Ependymal cells make up the epithelial monolayer that lines the brain ventricles and the spinal cord central canal that are filled with cerebrospinal fluid. The ependyma has several functions, including regulating solute exchange between the cerebrospinal fluid and parenchyma, controlling microcirculation of cerebrospinal fluid via coordinated ciliary beating, and acting as a partial barrier. Dysregulation of these functions can lead to waste clearance impairment, cerebrospinal fluid accumulation, hydrocephalus, and more. A role for ependymal cells in a variety of neurological disorders has been proposed, including in neuromyelitis optica and multiple sclerosis, two autoimmune demyelinating diseases of the central nervous system, where periventricular damage is common. What is not known is the mechanisms behind how ependymal cells become dysregulated in these diseases. In neuromyelitis optica, it is well established that autoantibodies directed against Aquaporin-4 are drivers of disease, and it has been shown recently that these autoantibodies can drive ependymal cell dysregulation. We propose a similar mechanism is at play in multiple sclerosis, where autoantibodies targeting a glial cell protein called GlialCAM on ependymal cells are contributing to disease. GlialCAM shares high molecular similarities with the Epstein–Barr virus (EBV) protein EBNA1. EBV has recently been shown to be necessary for multiple sclerosis initiation, yet how EBV mediates pathogenesis, especially in the periventricular area, remains elusive. In this perspective article, we discuss how ependymal cells could be targeted by antibody-related autoimmune mechanisms in autoimmune demyelinating diseases and how this is implicated in ventricular/periventricular pathology.

【 授权许可】

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Copyright © 2023 Bigotte, Groh, Marignier and Stratton.