INDUCTION OF ANTI-PURKINJE CELL ANTIBODIES IN-VIVO BY IMMUNIZING WITH A RECOMBINANT 52-KDA PARANEOPLASTIC CEREBELLAR DEGENERATION-ASSOCIATED PROTEIN

We immunized five different strains of mice with the recombinant human PCD17 protein, which is recognized by anti-Purkinje cell antibodies in the sera of patients with paraneoplastic cerebellar degeneration, and explored whether or not antibodies against cerebellar Purkinje cells could be induced in vivo. Autoantibodies against the cytoplasmic protein of Purkinje cells and other neurons were raised in all the strains of mice. These antisera stained the cytoplasm of the Purkinje cell in a coarse, granular pattern, but spared the nucleus. The antisera did not stain cerebellar granular cells. This pattern of immunostaining seen with the mouse antisera is similar to that seen with the human PCD sera, but more widespread cells in the central nervous system were stained with these antisera. The titers of the induced antibodies were comparable to or even higher than those of humans. The deposition of IgG was also demonstrated in the cytoplasm of Purkinje cells in the immunized mice. In spite of the generation of anti-Purkinje cell antibodies in vivo, neither clinical nor pathological changes consistent with cerebellar degeneration were detected 1 year following the first immunization.