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Keywords:

  • aquaporin 4 antibody;
  • astrocyte;
  • multiple sclerosis;
  • neuromyelitis optica;
  • neuromyelitis optica-immunoglobulin G

Abstract

Neuromyelitis optica (NMO) is characterized by severe optic neuritis and transverse myelitis. The relationship of NMO to multiple sclerosis (MS) has long been debated, but NMO has been classified as a demyelinating disease. Since the discovery of an NMO-specific autoantibody to aquaporin 4 (AQP4), a dominant water channel in the central nervous system densely expressed on end-feet of astrocytes, the clinical, magnetic resonance imaging and laboratory findings to distinguish NMO from MS have been clarified. Furthermore, pathological studies showed an extensive loss of immunoreactivities to astrocytic proteins, AQP4 and glial fibrillary acidic protein (GFAP), and perivascular deposition of immunoglobulins and activated complements with a relative preservation of the staining of myelin basic protein (MBP) in acute NMO lesions, but not in MS. In support of these pathological findings, the GFAP levels in the cerebrospinal fluid (CSF) during acute exacerbation of NMO are remarkably elevated compared with MBP and neurofilament, whereas the CSF-GFAP in MS is not different from those in controls. Additionally, recent experimental studies have convincingly shown that AQP4 antibody is pathogenic in causing astorocytic destruction and dysfunction in vitro, ex vivo and in vivo. These findings strongly suggest that damage of astrocytes is far more severe than those of myelin and neurons, and that autoimmune astrocytopathy is the primary pathology in NMO. Based on these accumulated data, we propose that NMO should be classified as an astrocytopathic disease rather than a demyelinating disease.