Purkinje cell antibodies in a patient with cerebellar disorder: detection of responsible antigenic proteins

Abstract

A 34-year-old male patient developed a neurological disorder and signs of cerebellar degeneration, with antibodies against Purkinje cells in the serum, a syndrome previously described as "paraneoplastic cerebellar atrophy". Antibody reaction of the patient's serum was demonstrated by immunohistochemistry on sections through the rat and human cerebellum. Purkinje cells demonstrated granular staining of cytoplasmic proteins and proximal dendrites with nuclear sparing. In an immunoblot, the antibodies from the patient's serum reacted with proteins from an extract of rat cerebellum. Only a few distinct proteins from the complex mixture of cerebellar proteins were found to bind with the serum antibodies when using a combination of affinity chromatography and sodium dodecyl sulphate (SDS) gel electrophoresis. The molecular masses of the proteins differed significantly from those identified in patients reported in the literature. Protein denaturation by SDS and 2-mercaptoethanol resulted in a decrease of antibody binding capacity. After immunosuppressive therapy and plasmapheresis, the reaction of the patient's serum with Purkinje cells was greatly diminished; however, only slight clinical improvement was observed. No sign of neoplasm could be found with repeated examinations. The immunological aspects of this case suggest that cerebellar degeneration may be linked to a previously unreported autoimmune response.