title: Autoantibodies in paraneoplastic cerebellar degeneration bind to cytoplasmic antigens of Purkinje cells in humans, rats and mice and are of multiple immunoglobulin classes.
abstract: Purkinje cell autoantibodies in sera of six female patients with paraneoplastic cerebellar degeneration (PCD) were investigated by indirect immunofluorescence for immunoglobulin isotype and species specificity. Four patients had gynecologic cancer, one breast cancer and one lymphoma. Control sera from 125 patients were negative for Purkinje cell antibodies of IgG, IgM and IgA isotypes. These included neurologically normal cancer patients, cancer patients with paraneoplastic syndromes not involving the cerebellum and patients with non-neoplastic neurologic disorders. IgG antibodies in the six PCD sera bound to discrete cells in the cerebellum of human, rat and mouse (titers 1000-128,000). Antibodies of IgM class were additionally found in two sera (titers 100 and 500) and IgA in a third serum (titer 1000). Antibodies of each isotype gave a similar staining pattern, highlighting the cytoplasm of Purkinje cells in a coarse granular pattern, and the peripheral cytoplasm of discrete molecular layer cells. Antibodies of IgE class were not found. Rodent cerebellar tissue was found to be a useful substitute for human tissue in clinical testing for Purkinje cell antibodies, and has the advantage of being readily available in highly viable state. Its use should facilitate further characterization of the autoantigen(s) of PCD, and possibly the development of an animal model involving passive transfer of immunoglobulins. Screening for IgM and IgA Purkinje cell antibodies in addition to IgG may increase the yield of positive results in clinical serological testing.
authors.affiliation: Mayo Medical School, Rochester, MN.
authors.forename: J L
authors.initials: JL
authors.lastname: Smith
authors.forename: J C
authors.initials: JC
authors.lastname: Finley
authors.forename: V A
authors.initials: VA
authors.lastname: Lennon
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002526:Cerebellar Diseases / Q000209:etiology / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology; D005260:Female; D005833:Genital Neoplasms, Female / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000145:classification / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology; D051379:Mice; D009410:Nerve Degeneration; D010257:Paraneoplastic Syndromes / Q000276:immunology*; D010266:Paraproteins / Q000276:immunology*; D011689:Purkinje Cells / Q000276:immunology*; D051381:Rats; D013045:Species Specificity
chemical_list: D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens; D007136:Immunoglobulins; D010266:Paraproteins