GLUTAMATE-RECEPTOR GLUR3 ANTIBODIES AND DEATH OF CORTICAL-CELLS

Rasmussen's encephalitis (RE), a childhood disease characterized by ep ileptic seizures associated with progressive destruction of a single c erebral hemisphere, is an autoimmune disease in which one of the autoa ntigens is a glutamate receptor, GluR3. The improvement of some affect ed children following plasma exchange that removed circulating GluR3 a ntibodies (anti-GluR3) suggested that anti-GluR3 gained access to the central nervous system where it exerted deleterious effects. Here, we demonstrate that a subset of rabbits immunized with a GluR3 fusion pro tein develops a neurological disorder mimicking RE. Anti-GluR3 IgG iso lated from serum of both ill and healthy GluR3-immunized animals promo ted death of cultured cortical cells by a complement-dependent mechani sm. IgG immunoreactivity decorated neurons and their processes in neoc ortex and hippocampus in ill but not in healthy rabbits. Moreover, bot h IgG and complement membrane attack complex (MAC) immunoreactivity wa s evident on neurons and their processes in the cortex of a subset of patients with RE. We suggest that access of IgG to epitopes in the cen tral nervous system triggers complement-mediated neuronal damage and c ontributes to the pathogenesis of both this animal model and RE.