UPTAKE OF SYSTEMICALLY ADMINISTERED HUMAN ANTICEREBELLAR ANTIBODY BY RAT PURKINJE-CELLS FOLLOWING BLOOD-BRAIN-BARRIER DISRUPTION

Paraneoplastic cerebellar degeneration accompanying gynecological or b reast malignancies is frequently associated with an autoantibody respo nse, termed ''type I'' or ''anti-Yo'' directed against cytoplasmic ant igens of cerebellar Purkinje cells. The role of this antibody response in the pathogenesis of paraneoplastic cerebellar degeneration is unkn own; however, it is also not known whether anti-Purkinje cell antibodi es from the systemic circulation bind to target Purkinje cell antigens under the conditions of brain inflammation and blood-brain barrier di sruption, which are frequently present at the onset of cerebellar symp toms. Inbred Lewis rats received intraperitoneal injections of type I or normal IgG in the setting of blood-brain barrier disruption induced by adoptive transfer of experimental allergic encephalomyelitis (EAE) and were killed after 24, 48, and 96 h. Brains of these animals were studied histologically for evidence of EAE and immunohistochemically f or binding of human or endogenous rat IgG to target neurons. Rat IgG w as detected around vessels and in Purkinje cells of all animals studie d. Human Ige was detected around vessels of all animals. In animals ex amined 96 h after receiving type I human IgG, human IgG was identified within processes of Purkinje cells and within occasional Purkinje cel l bodies. Uptake of type I IgG by other cell types was not observed, a nd neuronal uptake of IgG was not seen in brains of animals receiving normal human Igc. Our data demonstrate that circulating type I IgG is internalized by cerebellar Purkinje cells in the setting of blood-brai n barrier disruption and suggest a mechanism by which an antibody resp onse directed against cytoplasmic antigens of Purkinje cells may reach target antigens at the onset of paraneoplastic cerebellar degeneratio n.