Uptake of systemically administered human anticerebellar antibody by rat Purkinje cells following blood-brain barrier disruption.
Paraneoplastic cerebellar degeneration accompanying gynecological or breast malignancies is frequently associated with an autoantibody response, termed "type I" or "anti-Yo" directed against cytoplasmic antigens of cerebellar Purkinje cells. The role of this antibody response in the pathogenesis of paraneoplastic cerebellar degeneration is unknown; however, it is also not known whether anti-Purkinje cell antibodies from the systemic circulation bind to target Purkinje cell antigens under the conditions of brain inflammation and blood-brain barrier disruption, which are frequently present at the onset of cerebellar symptoms. 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 for binding of human or endogenous rat IgG to target neurons. Rat IgG was detected around vessels and in Purkinje cells of all animals studied. Human IgG was detected around vessels of all animals. In animals examined 96h after receiving type I human IgG, human IgG was identified within processes of Purkinje cells and within occasional Purkinje cell bodies. Uptake of type I IgG by other cell types was not observed, and neuronal uptake of IgG was not seen in brains of animals receiving normal human IgG. Our data demonstrate that circulating type I IgG is internalized by cerebellar Purkinje cells in the setting of blood-brain barrier disruption and suggest a mechanism by which an antibody response directed against cytoplasmic antigens of Purkinje cells may reach target antigens at the onset of paraneoplastic cerebellar degeneration.
Greenlee
J E
JE
Neurology Service, Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA.
Burns
J B
JB
Rose
J W
JW
Jaeckle
K A
KA
Clawson
S
S
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001812:Blood-Brain Barrier; D002531:Cerebellum / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D011689:Purkinje Cells / Q000378:metabolism*; D051381:Rats
D000906:Antibodies; D007074:Immunoglobulin G