Origins and immunopathogenesis of autoimmune central nervous system disorders

The field of autoimmune neurology is rapidly evolving, and recent discoveries have advanced our understanding of disease aetiologies. In this article, we review the key pathogenic mechanisms underlying the development of CNS autoimmunity. First, we review non-modifiable risk factors, such as age, se...

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Main Authors: Ramanathan, S, Brilot, F, Irani, SR, Dale, RC
Format: Journal article
Language:English
Published: Springer Nature 2023
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author Ramanathan, S
Brilot, F
Irani, SR
Dale, RC
author_facet Ramanathan, S
Brilot, F
Irani, SR
Dale, RC
author_sort Ramanathan, S
collection OXFORD
description The field of autoimmune neurology is rapidly evolving, and recent discoveries have advanced our understanding of disease aetiologies. In this article, we review the key pathogenic mechanisms underlying the development of CNS autoimmunity. First, we review non-modifiable risk factors, such as age, sex and ethnicity, as well as genetic factors such as monogenic variants, common variants in vulnerability genes and emerging HLA associations. Second, we highlight how interactions between environmental factors and epigenetics can modify disease onset and severity. Third, we review possible disease mechanisms underlying triggers that are associated with the loss of immune tolerance with consequent recognition of self-antigens; these triggers include infections, tumours and immune-checkpoint inhibitor therapies. Fourth, we outline how advances in our understanding of the anatomy of lymphatic drainage and neuroimmune interfaces are challenging long-held notions of CNS immune privilege, with direct relevance to CNS autoimmunity, and how disruption of B cell and T cell tolerance and the passage of immune cells between the peripheral and intrathecal compartments have key roles in initiating disease activity. Last, we consider novel therapeutic approaches based on our knowledge of the immunopathogenesis of autoimmune CNS disorders.
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spelling oxford-uuid:40d1f8b5-93d7-4f8c-931d-1e0d71b6597d2025-02-18T15:20:52ZOrigins and immunopathogenesis of autoimmune central nervous system disordersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:40d1f8b5-93d7-4f8c-931d-1e0d71b6597dEnglishSymplectic ElementsSpringer Nature2023Ramanathan, SBrilot, FIrani, SRDale, RCThe field of autoimmune neurology is rapidly evolving, and recent discoveries have advanced our understanding of disease aetiologies. In this article, we review the key pathogenic mechanisms underlying the development of CNS autoimmunity. First, we review non-modifiable risk factors, such as age, sex and ethnicity, as well as genetic factors such as monogenic variants, common variants in vulnerability genes and emerging HLA associations. Second, we highlight how interactions between environmental factors and epigenetics can modify disease onset and severity. Third, we review possible disease mechanisms underlying triggers that are associated with the loss of immune tolerance with consequent recognition of self-antigens; these triggers include infections, tumours and immune-checkpoint inhibitor therapies. Fourth, we outline how advances in our understanding of the anatomy of lymphatic drainage and neuroimmune interfaces are challenging long-held notions of CNS immune privilege, with direct relevance to CNS autoimmunity, and how disruption of B cell and T cell tolerance and the passage of immune cells between the peripheral and intrathecal compartments have key roles in initiating disease activity. Last, we consider novel therapeutic approaches based on our knowledge of the immunopathogenesis of autoimmune CNS disorders.
spellingShingle Ramanathan, S
Brilot, F
Irani, SR
Dale, RC
Origins and immunopathogenesis of autoimmune central nervous system disorders
title Origins and immunopathogenesis of autoimmune central nervous system disorders
title_full Origins and immunopathogenesis of autoimmune central nervous system disorders
title_fullStr Origins and immunopathogenesis of autoimmune central nervous system disorders
title_full_unstemmed Origins and immunopathogenesis of autoimmune central nervous system disorders
title_short Origins and immunopathogenesis of autoimmune central nervous system disorders
title_sort origins and immunopathogenesis of autoimmune central nervous system disorders
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