IgG-mediated cytotoxicity to myenteric plexus cultures in patients with paraneoplastic neurological syndromes

Autoantibodies against neuronal and tumour proteins have been described in many paraneoplastic neurological syndromes (PNS), but it is not clear wheth er these antibodies are pathogenic or simply a useful diagnostic tool. We t ook seven sera that were positive on routine screening for antineuronal ant ibodies and the IgG fractions. As controls we used sera from health blood-d onors, other neurological autoimmune diseases and patients with SCLC withou t PNS. We tested them on dissociated rat myenteric plexus cultures for cyto toxic effects. After incubation for 24 h, cytotoxicity was determined by a double fluorescence test (calcein green for living cells and ethidium homod imer-l for dead cells). We found an increased cell death rate in cultures i ncubated with the PNS sera, compared with all controls (P < 0.05). Isolated IgG fractions were also cytotoxic whereas the IgG-free serum fraction did not show any significant increase in cytotoxicity. After incubation with PN S IgG, FAGS analysis revealed an increased cytotoxicity rate only of the ne urones, but not the glial cells. Our results indicate that in PNS a complem ent-independent, antibody-mediated cytotoxicity against neurones may contri bute to the pathogenesis of these syndromes. (C) 2000 Academic Press.