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Open Access 01-05-2020 | Multiple Sclerosis | Original Paper

The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

Authors: Romana Höftberger, Yong Guo, Eoin P. Flanagan, A. Sebastian Lopez-Chiriboga, Verena Endmayr, Sonja Hochmeister, Damir Joldic, Sean J. Pittock, Jan Mendelt Tillema, Mark Gorman, Hans Lassmann, Claudia F. Lucchinetti

Published in: Acta Neuropathologica | Issue 5/2020

Abstract

We sought to define the pathological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) in an archival autopsy/biopsy cohort. We histopathologically analyzed 2 autopsies and 22 brain biopsies from patients with CNS inflammatory demyelinating diseases seropositive for MOG-antibody by live-cell-based-assay with full length MOG in its conformational form. MOGAD autopsies (ages 52 and 67) demonstrate the full spectrum of histopathological features observed within the 22 brain biopsies (median age, 10 years; range, 1–66; 56% female). Clinical, radiologic, and laboratory characteristics and course (78% relapsing) are consistent with MOGAD. MOGAD pathology is dominated by coexistence of both perivenous and confluent white matter demyelination, with an over-representation of intracortical demyelinated lesions compared to typical MS. Radially expanding confluent slowly expanding smoldering lesions in the white matter as seen in MS, are not present. A CD4+ T-cell dominated inflammatory reaction with granulocytic infiltration predominates. Complement deposition is present in all active white matter lesions, but a preferential loss of MOG is not observed. AQP4 is preserved, with absence of dystrophic astrocytes, and variable oligodendrocyte and axonal destruction. MOGAD is pathologically distinguished from AQP4-IgG seropositive NMOSD, but shares some overlapping features with both MS and ADEM, suggesting a transitional pathology. Complement deposition in the absence of selective MOG protein loss suggest humoral mechanisms are involved, however argue against endocytic internalization of the MOG antigen. Parallels with MOG-EAE suggest MOG may be an amplification factor that augments CNS demyelination, possibly via complement mediated destruction of myelin or ADCC phagocytosis.

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Title: The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody
Authors: Romana Höftberger
Yong Guo
Eoin P. Flanagan
A. Sebastian Lopez-Chiriboga
Verena Endmayr
Sonja Hochmeister
Damir Joldic
Sean J. Pittock
Jan Mendelt Tillema
Mark Gorman
Hans Lassmann
Claudia F. Lucchinetti
Publication date: 01-05-2020
Publisher: Springer Berlin Heidelberg
Keywords: Multiple Sclerosis
Autopsy
Neuromyelitis Optica Spectrum Disease
Demyelinating Disease
Pathology
Published in: Acta Neuropathologica / Issue 5/2020
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-020-02132-y

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The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

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rs4147929 variant minor allele increases ABCA7 gene expression and ABCA7 shows increased gene expression in Alzheimer’s disease patients compared with controls