0820 Antibody to aquaporin-4 (AQP4) as a marker of certain demyelinating diseases

AQP4 is the central nervous system’s predominant water channel protein, and while a direct pathophysiological relationship between antibodies to this protein and clinical disease has not been established, there is substantial evidence that this unique IgG antibody is a marker for a spectrum of neurological diseases. The antibody is also known as NMO-IgG, based on its association with neuromyelitis optica (NMO), an inflammatory demyelinating disease that principally targets the optic nerves and spinal cord, often leading to severe disability and occasionally to life-threatening respiratory failure. The spectrum of associated diseases has been expanded to include transverse myelitis without optic involvement, and recurrent optic neuritis without myelitis, and has also been useful in separating out diseases in this spectrum from similar or overlapping presentations of multiple sclerosis (which is important since treatment strategies will differ). The antibody may also be present in other autoimmune situations e.g. systemic lupus erythematosus where patients also have features of NMO; however NMO-IgG is not found in cases in which features of NMO are absent, suggesting that NMO is a coexisting entity and not a vasculopathic or other complication of SLE. These findings are not confined to adult patients, as demonstrated by a recent study of NMO-IgG involving patients in the USA and Argentina. Serological and clinical data were available for 58 children (mean age 12; range 4-18); 73% were non-Caucasian and 20 were of African origin. 57 had attacks of optic neuritis or transverse myelitis or both, and 26 had episodic cerebral symptoms ranging from encephalopathy to hiccoughs. 38 had brain MRI abnormalities, predominantly involving periventricular areas. Additional autoantibodies were detected in 76% of subjects tested, with several coexisting autoimmune disorders recorded (SLE, Sjogren’s syndrome, juvenile rheumatoid arthritis and Graves disease). Neurological attackes were recurrent in 54 patients, with significant numbers recording residual visual and/or motor disability.

Read more:
Neurology 2008, epub ahead of print (McKeon et al; CNS aquaporin-4 autoimmunity in children)
Arch Neurol 2008; 65: 78-83
Brain 2007; 130: 1206-23
Dis Markers 2006; 22: 197-206