Expression of the onconeural CV2/CRMP5 antigen in thymus and thymoma
Equipe d'Accueil 3062, Université Jean-Monnet, Saint-Etienne, France. Journal of Neuroimmunology
(Impact Factor: 2.47).
06/2006; 174(1-2):168-73. DOI: 10.1016/j.jneuroim.2006.01.018
Anti-CV2 antibodies (AB) react with the developmentally regulated neural proteins CRMPs and particularly with CRMP5. They occur with small cell lung cancer (SCLC) and thymoma. SCLCs universally express CRMP5. We investigated the expression of CRMPs in thymoma and thymus. In thymoma, none of the CRMPs were detected by immunohistochemistry in tumorous epithelial cells with specific antibodies including CRMP5 but an antibody reacting with a peptide common to the CRMPs labeled a 66-kDa protein in Western blot of rat brain, thymus, and thymoma extracts. Thus, the normal CRMP5 is probably not expressed by tumorous epithelial cells. These results indicate that the mechanisms leading to CRMP5 autoimmunization are different in SCLC and thymoma.
Available from: Svend Davanger
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ABSTRACT: We present a case with subacute limbic encephalitis (LE) and thymoma. Neither classical onconeural antibodies nor antibodies to voltage gated potassium channels (VGKC) were detected, but the serum was positive for anti-glutamic acid decarboxylase (GAD). The patient serum also stained synaptic boutons of pyramidal cells and nuclei of granule cells of rat hippocampus. The objective of the study was to identify new antibodies associated with LE. Screening a cDNA expression library identified collapsin response mediator protein 3 (CRMP3), a protein involved in neurite outgrowth. The serum also reacted with both CRMP3 and CRMP4 by Western blot. Similar binding pattern of hippocampal granule cells was obtained with the patient serum and rabbit anti-serum against CRMP1-4. The CRMP1-4 antibodies stained neuronal nuclei of a biopsy from the patient's temporal lobe, but CRMP1-4 expression in thymoma could only be detected by immunoblotting. Absorption studies with recombinant GAD failed to abolish the staining of the hippocampal granule cells. Our findings illustrate that CRMP3-4 antibodies can be associated with LE and thymoma. This has previously been associated with CRMP5.
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ABSTRACT: 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.
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