AUTOANTIBODIES TO GLUTAMATE-RECEPTOR SUBUNIT GLUR2 IN NONFAMILIAL OLIVOPONTOCEREBELLAR DEGENERATION

We describe a GS-year-old man with a 5-year history of progressive spo radic olivopontocerebellar atrophy (OPCA) who exhibits high serum tite rs of IgM autoantibodies to the neuronal glutamate receptor subunit GL uR2. Immunohistochemistry revealed intense staining of mouse cerebella r Purkinje cells and cells in the pontine nuclei and olivary complex. Glutamate receptor currents were activated in a subset of cultured mou se neurons by an anti-GluR2 IgM fraction, and they were blocked by the competitive AMPA-type glutamate receptor antagonist CNQX and by a syn thetic peptide to a specific epitope region of GluR2 (AA 369-393). The patient was treated with nine courses of plasmapheresis with little i mprovement of symptomatology. However, IgM titers to GluR2 decreased a pproximately 8-fold and the serum functional activity decreased propor tionally. These findings may suggest a role for autoimmunity to glutam ate receptors in the pathophysiology of certain forms of progressive n ervous system degeneration.