Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica.
Neuromyelitis optica (NMO) is a rare CNS inflammatory disorder that predominantly affects the optic nerves and spinal cord. Recent serological findings strongly suggest that NMO is a distinct disease rather than a subtype of multiple sclerosis. In NMO, serum antibodies, collectively known as NMO-IgG, characteristically bind to cerebral microvessels, pia mater and Virchow-Robin spaces. The main target antigen for this immunoreactivity has been identified as aquaporin-4 (AQP4). The antibodies are highly specific for NMO, and they are also found in patients with longitudinally extensive transverse myelitis without optic neuritis, which is thought to be a precursor to NMO in some cases. An antibody-mediated pathogenesis for NMO is supported by several observations, including the characteristics of the AQP4 antibodies, the distinct NMO pathology--which includes IgG and complement deposition and loss of AQP4 from spinal cord lesions--and emerging evidence of the beneficial effects of B-cell depletion and plasma exchange. Many aspects of the pathogenesis, however, remain unclear.
Jarius
Sven
S
Weatherall Institute of Molecular Medicine, University of Oxford, UK.
Paul
Friedemann
F
Franciotta
Diego
D
Waters
Patrick
P
Zipp
Frauke
F
Hohlfeld
Reinhard
R
Vincent
Angela
A
Wildemann
Brigitte
B
D000906:Antibodies / Q000097:blood*; D051401:Aquaporin 4 / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D006801:Humans; D009471:Neuromyelitis Optica / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D000906:Antibodies; D051401:Aquaporin 4