Paraneoplastic syndromes are believed to be immune-mediated disorders caused by the ectopic expression of a neuronal antigen in a non-neuronal cancer e.g. Lung or ovarian cancer. The immune system identifies the ectopically expressed neuronal antigen as """"""""foreign"""""""" and mounts an immune attack that affects both the cancer and the nervous system. Although rare, paraneoplastic syndromes are important neuroimmunologically, in that unlike multiple sclerosis, the causal antigens are known. The goal of this application is to understand the pathogenesis of paraneoplastic syndromes because such understanding may lead to more effective therapy of the neurologic disorder and the cancer that causes them. Understanding paraneoplastic syndromes may also help us better understand the pathogenesis of other neurologic autoimmune disorders such as multiple sclerosis. To achieve these goals, both clinical and laboratory investigations are planned. The investigators will continue to probe serum (and when available cerebrospinal fluid and tumor tissue) of patients suspected of suffering from paraneoplastic syndromes. To search for novel autoantibodies, they will continue to probe their serum bank, which contains over 3500 specimens of patients with cancer and/or putative paraneoplastic syndromes. The goal is to find new autoantibodies, discover if they are associated with a particular neurologic picture and with a particular underlying cancer. They will attempt to characterize the antigen(s) recognized by these antibodies by cloning their genes from central nervous system libraries. To compliment the antibody studies, patients suffering from paraneoplastic syndromes will be assayed for cytotoxic T-cells whose receptors recognize the paraneoplastic antigens. They will continue to search tumor and when available neural tissue to characterize the T-cell response in paraneoplastic disorders. In the clinic, they want to expand prospective analysis of patients with small cell lung cancer and add patients with Hodgkin's disease, testicular and ovarian cancer to discover how many harbor paraneoplastic autoantibodies and how that affects their neurologic status as well as the clinical course of their cancer. In addition to routine evaluation, antibody studies and haplotyping will be performed and the patients will be followed serially during treatment.
Showing the most recent 10 out of 44 publications
