Lennon et al. applied indirect immunofluorescence to mouse CNS tissue and found that 33/45 patients with NMO (73%) were seropositive with no false positives. The target antigen is aquaphorin 4 the dominant water channel in the CNS. It is located on the astrocyte foot processes ("glia limitans") right on the blood brain barrier. Several studies have shown aquaphorin loss in lesions in NMO patients. You get immune complex deposition, necrosis and cavitation that are vasculocentric. Aquaphorin-4 is not lost in MS.
Trigger antigen-- unknown. Binds aquaphorin, activates complement, which together with IL 8 and Il-17 recruit additional inflammatory cells and cause an intense inflammatory necrosis. There is no clonal expansion as antibody circulates in blood and notgenerated in CSF unlike MS. This may explain why NMo responds so well to plasmapheresis.
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