Carbonic anhydrase–related protein VIII: Autoantigen in paraneoplastic cerebellar degeneration

Serum of a patient with paraneoplastic cerebellar degeneration (PCD) and malignant melanoma had a unique reactivity with Purkinje cells that was not observed in serum of patients with PCD and other tumors, or with malignant melanoma without paraneoplastic syndromes. The screening of a human cerebellar complementary DNA expression library with the patient's serum resulted in the isolation of the CA8 gene. CA8 encodes carbonic anhydrase-related protein (CARP) VIII, preferentially expressed in Purkinje cells. The patient had intrathecal synthesis of CARP VIII antibodies. One of seven melanomas tested expressed CARP VIII. These data suggest CARP VIII may be an autoantigen involved in the pathogenesis of melanoma-associated PCD.