Heterogeneity of auto-antibodies against nAChR in myasthenic serum and their pathogenic roles in experimental autoimmune myasthenia gravis.

Many myasthenia gravis (MG) patients have auto-antibodies against the nicotinic acetylcholine receptor (nAChR), and monoclonal antibodies against the main immunogenic region (MIR) of nAChR can induce experimental autoimmune MG (EAMG). We investigated whether Fab fragment of MIR antibody (Fab35) could block the pathogenicity of polyclonal antibodies. Fab35 partially inhibited nAChR downmodulation, blocked EAMG serum-induced binding of polyclonal antibodies and complement deposition in vitro. Moreover, Fab35 did not ameliorate the EAMG serum-induced EAMG phenotype in rats. These results suggested that the EAMG serum possessed several different pathogenic antibodies that might be sufficient to induce the EAMG phenotype.