Antibodies to a subpopulation of glial cells and a 66 kDa developmental protein in patients with paraneoplastic neurological syndromes

BACKGROUND: Paraneoplastic neurological syndromes (PNS) are inflammatory disorders that probably depend on autoimmune processes. Several autoantibodies (anti-Hu, anti-Ri, and anti-Yo) have been characterised in PNS and proved to be helpful in the diagnosis. However, these do not account for all the cases and the possibility that other types of antibodies could be detected was investigated. METHODS AND RESULTS: Of 45 patients with PNS whose serum was probed on paraformaldehyde fixed rat brain sections, 11 patients were identified whose serum samples recognised a cytoplasmic antigen in a subpopulation of glial cells in the white matter of adult rat brainstem, cerebellum, and spinal cord that were double labelled with a monoclonal antibody specific for oligodendrocytes. All serum samples reacted with a 66 kDa protein of newborn rat brain on western blot analysis. These antibodies were designated as anti-CV2 antibodies. Only one of the 11 patients had one of the well characterised autoantibodies (anti-Hu). Five patients had cerebellar degeneration, three had limbic encephalitis, two had encephalomyelitis, and one had Lambert-Eaton myasthenic syndrome. The tumours were small cell lung cancer or undifferentiated mediastinal cancer in seven patients, uterine sarcoma in two, and malignant thymoma in two. Among 1061 control serum samples, only two patients had anti-CV2 antibodies. One had small cell lung cancer and the other malignant thymoma. CONCLUSIONS: The detection of anti-CV2 antibodies in patients with neurological disorders should be considered as an indication of the presence of an occult cancer.