Anti-GM2 IgM antibody-induced complement-mediated cytotoxicity in patients with dysimmune neuropathies

Anti-GM(2) IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome. To determine whether these antibodies can induce complement-dependent cytolysis we performed a cytotoxicity assay on neuroblastoma cells with sera from seven patients with demyelinating dysimmune neuropathies and high titers of anti-GM(2) IgM. As controls we used sera from seven patients with other anti-neural reactivities, six with the same neuropathies but no anti-GM(2) or other anti-neural reactivity and from eight normal subjects. Of the seven positive sera tested, six induced complement-mediated cytotoxicity, while none of the controls had any relevant effect on neuroblastoma cells. Preincubation of positive sera with purified GM(2) removed cytotoxic activity. Affinity purified anti-GM(2) IgM had the same cytotoxic effect of whole serum while serum or complement alone did not have any effect. In four anti-GM(2)-positive patients the percentage of cell lysis correlated with anti-GM(2) titers and with IgM staining of neuroblastoma cells while in two the cytotoxic effect was higher than expected from antibody titers. Complement-mediated cell lysis induced by anti-GM(2) IgM antibodies may be a possible mechanism of neural damage in patients with dysimmune neuropathy and high titers of anti-GM(2) IgM antibodies. (C) 2001 Elsevier Science B.V. All rights reserved.