Abstract
Prior to 1982, ovarian and certain other cancers were known to have a rare complication of progressive cerebellar ataxia, a disorder characterized pathologically by severe—often total—obliteration of cerebellar Purkinje cells. However, the cause of cerebellar injury in these patients was unknown. In that year, we began studies in which sera from individuals with this disorder were reacted with frozen sections of human cerebellum. These studies revealed that patients with ovarian cancer and cerebellar degeneration had high titers of antibodies directed against cytoplasmic antigens of Purkinje cells and deep cerebellar nuclei—a previously undescribed pattern of antibody response which was subsequently found not to be present in ovarian cancer patients who remained neurologically normal. This antibody, now known as “anti-Yo” or “anti-PCA1” provides a marker for rapidly progressive cerebellar ataxia and is heavily associated with gynecological and breast malignancies. Although the role of anti-Yo antibody in cerebellar injury has not been established in living animals, in vitro studies have demonstrated that anti-Yo antibody causes Purkinje cell death in the absence of T lymphocytes. In this commentary, we describe our studies leading to initial discovery of anti-Yo antibody, discuss the relationship of this discovery to current knowledge of paraneoplastic neurological disease, and outline some important questions which remain to be resolved before we fully understand the pathogenesis and optimal treatment of this disorder.
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Acknowledgements
Our work has been supported by Merit Review Awards from the United States Department of Veterans Affairs to (JG) and an award from the Western Institute for Biomedical Research (JG). All human materials were obtained and studied under Institutional Review Board (IRB) guidelines and in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. (University of Virginia, University of Utah and Veterans Affairs Salt Lake City Health Care System. JG and HB contributed equally to the preparation of this manuscript. Both authors have approved the submitted version.
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Greenlee, J.E., Brashear, H.R. The Discovery of Anti-Yo (Anti-PCA1) Antibody in Patients with Paraneoplastic Cerebellar Degeneration: Opening a Window into Autoimmune Neurological Disease. Cerebellum 22, 531–533 (2023). https://doi.org/10.1007/s12311-022-01446-9
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DOI: https://doi.org/10.1007/s12311-022-01446-9