Structure and functions of the molecules which are recognized by the anti-neural antibodies in paraneoplastic neurological syndrome

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Paraneoplasitic neurological syndrome is the remote effects of cancer on the nervous system which is the least common of the nonmetastatic complication of cancer. Present evidence suggests that some patients with paraneoplastic syndromes harbor autoantibodies in the serum and CSF that react with neuronal elements as well as with tumors.We isolated a cDNA clones "CZF" and "HuV" from a human brain library by immunoscreening using patients' sera and characterized them. We found that the clone "CZF" associated with paraneoplastic cerebellar degeneration (PCD) had zinc finger motives and the clone "HuV" associated with paraneoplastic sensory neuropathy had DNA binding sites and CAG triple repeats. These clones may affect transcription which is important to maintain neuronal cells. We made each recombinant partial protein, which was reacted by wech patient's serum, and produced antibody against each. Whole length cDNA cloning of "CZF" and "HuV" is still underway. We examined the effects of IgG from these and patient with anti-Hu antibody on cultured neuroblastoma cell line and found little effects in normal condition.We produced recombinant partial HuD protein, and established immunoblot and ELISA systems for detection of anti-Hu antibody in the serum and CSF of patients. These systems were useful for screening of cancer, especially of small cell lung cancer, and monitoring the effects of chemotherapy or recurrence of cancer.