Ultrastructural localization of anti-Purkinje cell antibody-binding sites in paraneoplastic cerebellar degeneration.

Abstract

Anti-Purkinje cell antibodies have been found specifically in patients with paraneoplastic cerebellar degeneration. We investigated the ultrastructural localization of antigen-antibody reaction products by means of immune electron microscopy, using an antibody identical to anti-Yo antibody, which occurs most frequently and which immunostains the cytoplasm of Purkinje cells. The antibody used here (anti-Us) was obtained from a patient with paraneoplastic cerebellar degeneration. Based on results indicating 94% homology between the amino acid sequences of the antigens recognized by anti-Us and anti-Yo antibodies, these two antigens are considered to be the same. After immunostaining of the specimen from the rat cerebellum by the avidin-biotin peroxidase complex method, ultrathin sections were examined with an electron microscope without counterstaining. Immunoreaction products were found to be localized on membrane-bound ribosomes and free ribosomes. There were no reaction products in the endoplasmic reticulum lumen, smooth endoplasmic reticulum, Golgi complex, mitochondria, or nucleus. Although it has been noted that there is a leucine-zipper motif in the amino acid sequence of the antigenic protein that can bind to DNA, our findings indicate that this protein exists on the ribosome and may regulate protein synthesis rather than gene expression in the nucleus.