Passive transfer and active immunization with the recombinant leucine-zipper (Yo) protein as an attempt to establish an animal model of paraneoplastic cerebellar degeneration

Abstract

Passive transfer of paraneoplastic cerebellar degeneration (PCD) IgG to rodents as well as active immunization with recombinant Yo fusion protein were tried in order to examine the roles of anti-Purkinje cell antibody (anti-Yo antibody) present in the sera and cerebrospinal fluid of patients with PCD in Purkinje cell loss, the hall mark of PCD pathology. On a single injection of PCD IgG to mouse brain, IgG was taken into Purkinje cells and remained there for more than 36 h without Purkinje cell loss. Injection of PCD IgG together with complement or lipopolysaccharide-activated human macrophages or rat mononuclear cells to rats ventricles did not cause Purkinje cell loss. We made a recombinant Yo fusion protein that has the leucine-zipper protein (Yo protein), the common epitope for anti-Yo antibody. Mice immunized with this Yo protein produced high titer antibody against it for more than 3 months, during which time neither neurological symptoms nor Purkinje cell loss occurred. The anti-Yo antibody, with or without complement or activated mononuclear cells, therefore could not be the sole cause of Purkinje cell loss.