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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 LambertEaton 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

The Neurotrophic factor gdnf plays diverse developmental roles, supporting survival and also acting as a chemoattractant for axon and cell migration. We report that in the developing spinal cord, a focal source of gdnf is present in the floor plate (FP) where commissural axons cross the midline. Gdnf has no direct guidance properties but switches on the responsiveness of crossing commissural growth cones to the midline repellent Semaphorin3B by suppressing calpain-mediated processing of the Sema3B signaling coreceptor Plexin-A1. Analysis of single and double mutant mouse models indicates that although gdnf is the principal trigger of Sema3B midline repulsion, it acts with another FP cue, NrCAM. Finally, genetic and in vitro experiments provide evidence that this gdnf effect is RET independent and mediated by NCAM/GFRα1 signaling. This study identifies a regulator of midline crossing and reveals interplays between Semaphorin and gdnf signaling during axon guidance.