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 whether these antibodies are pathogenic or simply a useful diagnostic tool. We took seven sera that were positive on routine screening for antineuronal antibodies and the IgG fractions. As controls we used sera from health blood-donors, other neurological autoimmune diseases and patients with SCLC without PNS. We tested them on dissociated rat myenteric plexus cultures for cytotoxic effects. After incubation for 24 h, cytotoxicity was determined by a double fluorescence test (calcein green for living cells and ethidium homodimer-1 for dead cells). We found an increased cell death rate in cultures incubated 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 PNS IgG, FACS analysis revealed an increased cytotoxicity rate only of the neurones, but not the glial cells. Our results indicate that in PNS a complement-independent, antibody-mediated cytotoxicity against neurones may contribute to the pathogenesis of these syndromes.