Autoimmune & Demyelinating
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.
Introduction
- Central nervous system (CNS) demyelination occurs when the myelin responsible for the insulation of axons is damaged, resulting in poor conduction of action potentials, impaired neuronal signalling and, in some cases, partial or complete neuronal loss.
- Adaptive immunity enables a rapid and intensive response against subsequent exposures to previously encountered antigens. B and T lymphocytes are the key mediators of this branch of the immune system and are responsible for the humoral and cell-mediated adaptive immune response, respectively.
- Antibodies or immunoglobulins (Igs) are specialised proteins produced by B cells with a precise affinity and specificity for their target antigen.
- Historically, the brain and spinal cord were perceived as immune-privileged sites, lacking the conventional lymphatic system accessible to the remainder of the body.
- Recent decades have shed light upon the complexity of ongoing immune trafficking across the blood–brain and blood–cerebrospinal fluid (CSF) barriers.
- This intricate interplay between the CNS and the immune system has highlighted the notion that certain neurological demyelinating disorders are attributable to an inflammatory autoimmune pathophysiology.
- In this review, we explore the complex role of autoimmunity in CNS demyelinating disorders, namely multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).
- Firstly, we investigate the similarities and differences in the clinical characteristics and pathologies between the three disease entities.
- We then consider hypotheses regarding the autoimmune aetiology of these disorders and the mechanisms involved in disease pathogenesis.
- Lastly, we discuss trends in the diagnosis and therapy of these disorders as well as future directions in the field of autoimmune demyelination.