The paraneoplastic neurologic diseases (PND's) are a diverse group of neurological disorders arising in the setting of cancer that are believed to have an immunological basis. It is believed that the disorders are triggered when systemic tumors express proteins normally made only in neurons, leading to effective anti-tumor immunity and autoimmune neuronal degeneration. We have utilized high titer antibodies present in the serum and CSF of PND patients to classify the disorders and identify the target antigens. However, treatment protocols that reduce antibody titers show no clinical response, and passive transfer of antibody or induction of antibody responses in animals do not reproduce the disorders. We propose to explore the contribution of B and T cells to the clinical disorder; in particular, we suspect and will specifically search for a previously unidentified T cell component to the disease. In preliminary studies, we have been able to find evidence for a specific cytotoxic T cell immune response in the serum and spinal fluid of several PND patients. We will attempt to modify the autoimmune response in order to improve clinical outcome, monitoring both clinical and immunological parameters.
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