ABSTRACT
Paraneoplastic cerebellar degeneration (PCD) is often associated with Yo antibodies that are directed against human cerebellar degeneration-related protein 2 (CDR2). Such antibodies may also be found in ovarian cancer patients without PCD. We studied if there was an association between Yo antibody production and differences in CDR2 cDNA sequence, mRNA or CDR2 expression in ovarian cancers. We found similar CDR2 cDNA sequence, mRNA and protein levels in primary ovarian cancers, with or without associated Yo antibodies. CDR2 was also present in other cancers, as well as in normal ovary tissue. The results suggest that Yo antibodies are not only related to the expression of CDR2 alone, but also to immune dysregulation.
Subject(s)
Antibodies/analysis , Antibodies/immunology , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/immunology , Ovarian Neoplasms/immunology , Adult , Aged , Antigen-Antibody Complex/immunology , Female , Humans , Middle Aged , Nerve Tissue Proteins/genetics , Ovarian Neoplasms/genetics , Paraneoplastic Cerebellar Degeneration/immunology , RNA, Messenger/geneticsABSTRACT
The collapsin response mediator protein 5 (CRMP5) antibody is usually associated with paraneoplastic neurological syndrome (PNS) and small-cell lung cancer (SCLC) or thymoma. The objective of this study was to assess the frequency of CRMP5 antibodies in patients with such tumours and to see if the presence of antibodies was associated with prognosis in these cancers. A multi-well adapted immunoprecipitation assay using radiolabelled recombinant CRMP5 protein, produced by coupled in vitro transcription/translation, was used for the detection of CRMP5 antibodies. Sera from 200 patients with SCLC, 73 patients with thymoma and myasthenia gravis (MG) and from 300 healthy blood donors were examined for CRMP5 antibodies. Positive sera were also examined by immunofluorescence and immune blots. The serological results were compared with disease severity of the patients with thymoma or SCLC. CRMP5 antibodies were detected in 10/200 (5%) of the SCLC, 9/73 (12%) of the thymomas and in 2/300 (0.6%) of the healthy controls by immunoprecipitation. The antibodies were less frequently detected by immunofluorescence or immune blots. There was no significant correlation between CRMP5 antibodies and disease severity. CRMP5 antibodies are more than twice as frequent, and the antibody levels are higher in patients with thymoma and MG than in patients with SCLC. The antibodies are correlated to these tumours, but not to disease severity.
Subject(s)
Antibodies/blood , Carcinoma, Small Cell/blood , Lung Neoplasms/blood , Nerve Tissue Proteins/immunology , Thymoma/blood , Thymus Neoplasms/blood , Adult , Aged , Biomarkers, Tumor/blood , Carcinoma, Small Cell/mortality , Female , Fluorescent Antibody Technique , Humans , Hydrolases , Immunoblotting , Immunoprecipitation , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Male , Microtubule-Associated Proteins , Middle Aged , Myasthenia Gravis/blood , Prognosis , Sensitivity and Specificity , Thymoma/mortality , Thymus Neoplasms/mortalityABSTRACT
The presence of circulating antineuronal antibodies has been associated with paraneoplastic neurological syndromes (PNS). Ri antibodies are often associated with lung or breast cancer, but the prevalence of such antibodies in large cancer materials is largely unknown. We used a highly sensitive immunoprecipitation assay to study the level of Ri antibodies in blood samples from 200 patients with small cell lung cancer (SCLC), 253 patients with breast cancer and 557 patients with ovarian cancer. Two hundred blood donors and six Ri positive PNS patients served as controls. The recombinant antigen used in the immunoprecipitation assay was radiolabeled by a coupled in vitro transcription and translation (ITT) technique, enabling low levels of antibodies to be detected. None of the blood donors contained Ri antibodies, whereas all of the sera from the PNS patients were positive. Ri antibodies were present in 4.5% of the patients with SCLC, 0.8% of the patients with breast cancer and in 0.2% of the patients with ovarian cancer. Retesting of the Ri positive samples with immunofluorescense and immune blot showed that the immunoprecipitation technique was more sensitive than the other immune assays. Ri antibodies were not associated with PNS in the patients with breast or ovarian cancer. Neurological data were not available for the SCLC patients, but in these, Ri antibodies were not associated with survival.
Subject(s)
Antibodies/blood , Antigens, Neoplasm/immunology , Immunoprecipitation/methods , Neoplasms/blood , Neoplasms/immunology , Nerve Tissue Proteins/immunology , Paraneoplastic Syndromes/diagnosis , RNA-Binding Proteins/immunology , Blotting, Western , Breast Neoplasms/blood , Breast Neoplasms/immunology , Breast Neoplasms/mortality , Carcinoma, Small Cell/blood , Carcinoma, Small Cell/immunology , Female , Fluorescent Antibody Technique , Humans , Immunoblotting , Lung Neoplasms/blood , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Neoplasms/mortality , Neuro-Oncological Ventral Antigen , Ovarian Neoplasms/blood , Ovarian Neoplasms/immunology , Ovarian Neoplasms/mortality , Paraneoplastic Syndromes/blood , Paraneoplastic Syndromes/immunology , Sensitivity and Specificity , Survival AnalysisABSTRACT
Patients with paraneoplastic neurological syndromes often produce intrathecal antibodies. We have employed isoelectric focusing and peroxidase-labeled anti-IgG or 35S-labeled Hu or Yo antigens to identify oligoclonal bands (OCB) representing either total IgG or Hu or Yo antibodies in serum and CSF of patients with paraneoplastic encephalomyelitis (PEM) or paraneoplastic cerebellar degeneration (PCD). OCBs representing paraneoplastic antibodies were found in all CSF, but in only three sera. Yo antibodies represented the majority of IgG bands in PCD-CSF, which may reflect a limited immune response, whereas in PEM/SN, there were numerous additonal IgG bands of unknown specificity, indicating a broader immune response in these patients.
