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B cell rich meningeal inflammation associates with increased spinal cord pathology in multiple sclerosis

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Title: B cell rich meningeal inflammation associates with increased spinal cord pathology in multiple sclerosis
Authors: Reali, C
Magliozzi, R
Roncaroli, F
Nicholas, R
Howell, OW
Reynolds, R
Item Type: Journal Article
Abstract: Increased inflammation in the cerebral meninges is associated with extensive subpial cortical grey matter pathology in the forebrain and a more severe disease course in a substantial proportion of secondary progressive multiple sclerosis (SPMS) cases. It is not known whether this relationship extends to spinal cord pathology. We assessed the contribution of meningeal and parenchymal immune infiltrates to spinal cord pathology in SPMS cases characterised by the presence (F+) or absence (F‐) of lymphoid‐like structures in the forebrain meninges. Transverse cryosections of cervical, thoracic and lumbar cord of 22 SPMS and 5 control cases were analysed for CD20+ B cells, CD4+ and CD8+ T cells, microglia/macrophages (IBA‐1+), demyelination (myelin oligodendrocyte glycoprotein+) and axon density (neurofilament‐H+). Lymphoid‐like structures containing follicular dendritic cell networks and dividing B cells were seen in the spinal meninges of three out of 11 F+SPMS cases. CD4+ and CD20+ cell counts were increased in F+SPMS compared to F‐SPMS and controls, whilst axon loss was greatest in motor and sensory tracts of the F+SPMS cases (p<0.01). The density of CD20+ B cells of the spinal leptomeninges correlated with: CD4+ T cells and total B and T cells of the meninges; with the density of white matter perivascular CD20+ and CD4+ lymphocytes (p<0.05); with white matter lesion area (p<0.05); and the extent of axon loss (p<0.05) in F+SPMS cases only. We show that the presence of lymphoid‐like structures in the forebrain is associated with a profound spinal cord pathology, and local B cell rich meningeal inflammation associates with the extent of cord pathology. Our work supports a principal role for B cells in sustaining inflammation and tissue injury throughout the CNS in the progressive disease stage.
Issue Date: Jul-2020
Date of Acceptance: 20-Dec-2019
URI: http://hdl.handle.net/10044/1/77840
DOI: 10.1111/bpa.12841
ISSN: 1015-6305
Publisher: Wiley
Start Page: 779
End Page: 793
Journal / Book Title: Brain Pathology
Volume: 30
Issue: 4
Copyright Statement: © 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Multiple Sclerosis Society
Parkinson's UK
Funder's Grant Number: 0747/02
J-1402
Keywords: Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Pathology
Neurosciences & Neurology
axon loss
B-cell follicle
demyelination
lymphoid-like structures
AXONAL LOSS
CORTICAL PATHOLOGY
MATTER DEMYELINATION
NEURONAL LOSS
DISABILITY
GRADIENT
DISEASE
NEURODEGENERATION
OCRELIZUMAB
FOLLICLES
B-cell follicle
axon loss
demyelination
lymphoid-like structures
Neurology & Neurosurgery
1103 Clinical Sciences
1109 Neurosciences
Publication Status: Published
Open Access location: https://doi.org/10.1111/bpa.12841
Online Publication Date: 2020-04-03
Appears in Collections:Faculty of Medicine
Department of Brain Sciences