Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neurone degeneration following paraneoplastic Yo antibody internalization and binding to cerebellar degeneration-related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D<sub>28k</sub> malfunction.
Cerebellar degeneration-related protein 2 (CDR2) has been presumed to be the main antigen for the onconeural antibody Yo, which is strongly associated with ovarian cancer and paraneoplastic cerebellar degeneration (PCD).
In the course of modeling the naturally occurring tumor immunity seen in patients with paraneoplastic cerebellar degeneration (PCD), we discovered an unexpectedly high threshold for breaking CD8+ cytotoxic T cell (CTL) tolerance to the PCD autoantigen, CDR2.
Paraneoplastic cerebellar degeneration (PCD) is often associated with Yo antibodies that are directed against human cerebellar degeneration-related protein 2 (CDR2).
Eight patients with paraneoplastic cerebellar degeneration (PCD) and anti-Yo antibodies were investigated to determine whether there is any association between cytotoxic T lymphocyte (CTL) responses reactive with two previously defined Yo-derived, HLA-A2.1 restricted epitopes (cdr2-1 and cdr2-2) and the presence of tumour-infiltrating CD8+ CTLs. cdr2-1 and cdr2-2-specific CTL responses could not be detected in 5 HLA-A2.1(+) patients in an ex vivo interferon-gamma ELISPOT assay and only 2/9 tumour sections contained CD8(+) intratumoural lymphocytes suggesting a very limited role for CTL-mediated tumour immunity in this patient group, all of whom had evidence of widespread malignancy at the time of diagnosis and/or death.
Paraneoplastic cerebellar degeneration associated with gynecological and breast malignancies (PCD) is known to develop autoantibodies and autoreactive cytotoxic T lymphocytes (CTLs) specific for a cytoplasmic protein of Purkinje cells PCD17/cdr2, in the blood of patients.
Paraneoplastic cerebellar degeneration (PCD) is a disorder in which breast or ovarian tumors express an onconeural antigen termed cdr2, which normally is expressed in cerebellar Purkinje neurons.
Paraneoplastic cerebellar degeneration (PCD) is a disorder in which breast or ovarian tumors express an onconeural antigen termed cdr2, which normally is expressed in cerebellar Purkinje neurons.
A post-transcriptional regulatory mechanism restricts expression of the paraneoplastic cerebellar degeneration antigen cdr2 to immune privileged tissues.