Autoantibodies to Glutamate Receptor GluR3 in Rasmussen's Encephalitis

TLDR

Rasmussen's encephalitis is a progressive childhood disease of unknown cause characterized by severe epilepsy, hemiplegia, dementia, and inflammation of the brain. The authors immunized rabbits with recombinant GluR3 protein, inducing seizure‑like behaviors and histopathologic changes resembling Rasmussen's encephalitis. Serum antibodies to GluR3 correlate with Rasmussen's encephalitis, and transient reduction of these antibodies by plasma exchange lowered seizure frequency and improved neurological function, indicating that GluR3 is an autoantigen and that an autoimmune mechanism may drive the disease.

Abstract

Rasmussen's encephalitis is a progressive childhood disease of unknown cause characterized by severe epilepsy, hemiplegia, dementia, and inflammation of the brain. During efforts to raise antibodies to recombinant glutamate receptors (GluRs), behaviors typical of seizures and histopathologic features mimicking Rasmussen's encephalitis were found in two rabbits immunized with GluR3 protein. A correlation was found between the presence of Rasmussen's encephalitis and serum antibodies to GluR3 detected by protein immunoblot analysis and by immunoreactivity to transfected cells expressing GluR3. Repeated plasma exchanges in one seriously ill child transiently reduced serum titers of GluR3 antibodies, decreased seizure frequency, and improved neurologic function. Thus, GluR3 is an autoantigen in Rasmussen's encephalitis, and an autoimmune process may underlie this disease.