Cytotoxic effect of neuromyelitis optica antibody (NMO-IgG) to astrocytes: an in vitro study.

NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) that binds selectively to aquaporin-4 (AQ4), an astrocytic water channel. The normal distribution of AQP4 coincides with the sites of immunoglobulin and complement deposits in lesions found in autopsy studies. The underlying mechanisms of cytotoxicity by NMO-IgG on astrocytes are not well known. In this study we show that serum samples from seropositive NMO patients (21) induce a higher rate of cell death compared with sera from seronegative NMO (16), relapsing-remitting MS (20) patients, and healthy controls (24) on primary cultures of astrocytes. Similar results were obtained by two different techniques: lactate dehydrogenase release and tetrazolium-based viability assay. Cell death was only observed in the presence of active complement. The complement-dependent cytotoxicity was not accompanied by caspase-3/7 activation or increase in the percentage of apoptotic cells. Our data show that NMO-IgG induces a complement-dependent cytotoxicity of astrocytes in vitro, and suggest that a mechanism of cellular death by necrosis might be implicated in the pathophysiology of NMO.