title: Purkinje cell death after uptake of anti-Yo antibodies in cerebellar slice cultures.
abstract: Paraneoplastic cerebellar degeneration accompanying gynecological and breast cancers is characteristically accompanied by a serum and cerebrospinal fluid (CSF) antibody response, termed "anti-Yo," which reacts with cytoplasmic proteins of cerebellar Purkinje cells. Because these antibodies interact with cytoplasmic rather than cell surface membrane proteins, their role in causing Purkinje cell death has been questioned. To address this issue, we studied the interaction of anti-Yo antibodies with Purkinje cells in slice (organotypic) cultures of rat cerebellum. We incubated cultures with immunoglobulin G (IgG)-containing anti-Yo antibodies using titers of anti-Yo antibody equivalent to those found in CSF of affected patients. Cultures were then studied in real time and after fixation for potential uptake of antibody and induction of cell death. Anti-Yo antibodies delivered in serum, CSF, or purified IgG were taken up by viable Purkinje cells, accumulated intracellularly, and were associated with cell death. Normal IgG was also taken up by Purkinje cells but did not accumulate and did not affect cell viability. These findings indicate that autoantibodies directed against intracellular Purkinje cell proteins can be taken up to cause cell death and suggest that anti-Yo antibody may be directly involved in the pathogenesis of paraneoplastic cerebellar degeneration.
authors.affiliation: Neurology Service, George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA. john.greenlee@hsc.utah.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Greenlee
authors.forename: Susan A
authors.initials: SA
authors.lastname: Clawson
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Hill
authors.forename: Blair L
authors.initials: BL
authors.lastname: Wood
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tsunoda
authors.forename: Noel G
authors.initials: NG
authors.lastname: Carlson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000166:cytology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000633:toxicity; D020287:In Situ Nick-End Labeling / Q000379:methods; D018613:Microscopy, Confocal / Q000379:methods; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009924:Organ Culture Techniques; D009930:Organic Chemicals; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
chemical_list: C095184:CDR2 protein, human; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D009930:Organic Chemicals; C402795:SYTOX Green