Molecular Pathogenesis of Neuromyelitis Optica
Open Access
- 10 October 2012
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 13 (10), 12970-12993
- https://doi.org/10.3390/ijms131012970
Abstract
Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS) when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6) have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies.Keywords
This publication has 153 references indexed in Scilit:
- Aquaporin 4‐specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporterAnnals of Neurology, 2012
- Consequences of NMO-IgG binding to aquaporin-4 in neuromyelitis opticaProceedings of the National Academy of Sciences, 2012
- Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytesProceedings of the National Academy of Sciences, 2011
- Deciphering the role of Th17 cells in human diseaseTrends in Immunology, 2011
- Ex vivo spinal cord slice model of neuromyelitis optica reveals novel immunopathogenic mechanismsAnnals of Neurology, 2011
- Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis opticaProceedings of the National Academy of Sciences, 2011
- Evidences for a Leaky Scanning Mechanism for the Synthesis of the Shorter M23 Protein Isoform of Aquaporin-4Journal of Biological Chemistry, 2010
- Astrocytes: biology and pathologyActa Neuropathologica, 2009
- Intrathecal pathogenic anti–aquaporin‐4 antibodies in early neuromyelitis opticaAnnals of Neurology, 2009
- Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cellsNature, 2006