Neuromyelitis Optica Spectrum Disorders, Immunology of

Neuromyelitis optica (NMO) constitutes a spectrum of inflammatory autoimmune demyelinating disorders of the central nervous system, which is clinically, pathologically, and pathophysiologically distinct from multiple sclerosis. It is unified by an immunoglobulin G (IgG) biomarker (NMO-IgG) targeting the water channel aquaporin-4. In vitro, NMO-IgG binds to the extracellular domain of astrocytic aquaporin-4 causing partial internalization, complement activation, disruption of water and glutamate homeostasis, and inflammatory sequelae. Injection of NMO-IgG into rodents with disrupted blood-brain barrier recapitulates distinctive neuropathological findings of NMO. The aims of current optimal therapies for NMO spectrum disorders are to deplete antibody and reduce inflammation in the acute phase, and thereafter to prevent relapses by maintaining immunosuppressant therapy for at least 5 years.