Autoimmunity to Munc-18 in Rasmussen's encephalitis

Rasmussen's encephalitis (RE) is a rare disease of the central nervous syst em characterized by severe epileptic seizures, progressive degeneration of a single cerebral hemisphere, and autoimmunity directed against glutamate r eceptor subunit, GluR3. We report here the identification of high-titer aut oantibodies directed against munc-18 in the serum of a single patient with RE previously shown to have anti-GluR3 antibodies. Munc-18 is an intracellu lar protein residing in presynaptic terminals, which is required for secret ion of neurotransmitters. These findings are consistent with the possibilit y of intermolecular epitope spreading between GluR3, a postsynaptic cell su rface protein, and munc-18, a presynaptic intracellular protein. Immune att ack on these two proteins, which participate at distinct steps of synaptic transmission, could act in an additive or synergistic manner to impair syna ptic function and lead to seizures and neuronal death.