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Review
. 2021 Jul 26;10(7):e1316.
doi: 10.1002/cti2.1316. eCollection 2021.

Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease

Joseph A Lopez  1   2 , Martina Denkova  1   3 , Sudarshini Ramanathan  1   4   5 , Russell C Dale  1   2   4   6 , Fabienne Brilot  1   2   3   6
Affiliations
Review

Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease

Joseph A Lopez et al. Clin Transl Immunology. .

Abstract

Autoimmunity plays a significant role in the pathogenesis of demyelination. Multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are now recognised as separate disease entities under the amalgam of human central nervous system demyelinating disorders. While these disorders share inherent similarities, investigations into their distinct clinical presentations and lesion pathologies have aided in differential diagnoses and understanding of disease pathogenesis. An interplay of various genetic and environmental factors contributes to each disease, many of which implicate an autoimmune response. The pivotal role of the adaptive immune system has been highlighted by the diagnostic autoantibodies in NMOSD and MOGAD, and the presence of autoreactive lymphocytes in MS lesions. While a number of autoantigens have been proposed in MS, recent emphasis on the contribution of B cells has shed new light on the well-established understanding of T cell involvement in pathogenesis. This review aims to synthesise the clinical characteristics and pathological findings, discuss existing and emerging hypotheses regarding the aetiology of demyelination and evaluate recent pathogenicity studies involving T cells, B cells, and autoantibodies and their implications in human demyelination.

Keywords: AQP4 antibody; MOG antibody; autoimmune demyelination; multiple sclerosis; neuromyelitis optica spectrum disorders; pathology.

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Conflict of interest statement

JAL reports funding from the Research Training Program Scholarship (Australia). SR has received competitive research funding from the National Health and Medical Research Council (Australia), the Petre Foundation (Australia), the Brain Foundation (Australia), the Royal Australasian College of Physicians and the University of Sydney; and is currently supported by an NHMRC Early Career Fellowship (APP1141169). SR is a consultant on an advisory board for UCB and Limbic Neurology and has received honoraria from Biogen and Limbic Neurology as an invited speaker. RCD and FB have received research funding from The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia, the Petre Foundation and the National Health Medical Research Council (Australia). They have received honoraria from Biogen Idec and Merck as invited speakers. MD declares no competing interests.

Figures

Figure 1
Figure 1
Pathological features of lesions in autoimmune demyelination. Demyelinating lesions commonly consist of immune cell infiltrates predominated by activated macrophages and microglia, lymphocytes, and varying degrees of immunoglobulin and complement deposition. CD4+ T cells outnumber CD8+ T cells in MOGAD and NMOSD while CD8+ T cells predominate in MS. Granulocytic infiltration is seen in MOGAD and NMOSD while not frequently observed in MS lesions. Axon and astrocyte loss is profound in NMOSD while astrocytes and axons are largely preserved in MS and MOGAD. AQP4 downregulation is observed in NMOSD while conflicting reports of MOG internalisation have been seen in MOGAD. Ab, antibody; AQP4, aquaporin‐4 water channel; Ig, immunoglobulin; MOG, myelin oligodendrocyte glycoprotein; MOGAD, MOG Ab‐associated disease; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorders.
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