Paraneoplastic antibodies against HuD detected by a sensitive radiobinding assay

Storstein, Anette; Monstad, Sissel E.; Nakkestad, Hanne Linda; Husebye, Eystein S.; Vedeler, Christian A.

doi:10.1007/s00415-004-0303-9

Cited by 15 publications

(7 citation statements)

References 23 publications

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“…This speculation is supported by the finding that only a subgroup of the patients positive in the RIA assay showed reactivity in Western blot. RIA seems to be a more sensitive method for detecting autoantibodies, similar to the findings with anti-Hu (Storstein et al , 2004) and antiinsulin (Sodoyez-Goffaux et al , 1988). Five of the lung cancer patients positive for anti-PDXP also had circulating Hu-antibodies but not clinically evident PND.…”

Section: Discussionsupporting

confidence: 67%

Pyridoxal phosphatase is a novel cancer autoantigen in the central nervous system

et al. 2004

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Autoantibodies against many proteins are common in sera from patients with various types of cancer. These antibodies are sometimes involved in the development of conditions associated with cancer, such as paraneoplastic neurologic disorders. We used a human brain cDNA expression library and serum from a paraneoplastic neurologic disorder patient to search for new autoantigens in the nervous system. Pyridoxal phosphatase was identified as a novel autoantigen. Expression studies showed that pyridoxal phosphatase was strongly expressed in various parts of the central nervous system. Sera contained antibodies against pyridoxal phosphatase in 22 of 243 (9.1%) patients with lung cancer and eight of 113 (7.1%) with other forms of cancer vs two of 88 (2.3%) healthy control subjects. In addition, 2–4% of patients with different autoimmune diseases had autoantibodies against pyridoxal phosphatase. None of the antipyridoxal phosphatase-positive patients were known to have a paraneoplastic neurologic disorder. Hence, autoantibodies against pyridoxal phosphatase correlate with cancer but not necessarily with the subset of patients with paraneoplastic neurological disorders although serum from such a patient was used to screen the cDNA library. This study showed that yet another enzyme involved in pyridoxal 5′-phosphate metabolism is an autoantigen. Thus, pyridoxal 5′-phosphate seems to be a common denominator for autoantigens involved in autoimmune diseases.

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Section: Discussionsupporting

confidence: 67%

Pyridoxal phosphatase is a novel cancer autoantigen in the central nervous system

et al. 2004

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“…Finally, fluid‐phase assays probably have some advantage over solid‐phase assays as some common autoantibodies are not reliable detected by solid‐phase assays [16,17]. As the results from the different techniques employed were more comparable in detecting Hu antibodies [8,11], we suspect that the cdr2‐protein has conformational epitopes as well as linear epitopes.…”

Section: Discussionmentioning

confidence: 99%

“…MultiScreen 96‐well filtration plates (MABV N0B50, Millipore, Bedford, MA, USA), which allow high throughput analysis, were used for immunoprecipitation experiments. Each well was washed and blocked as previously described [11]. Radiolabelled cdr2 protein (30 000 cpm/well) and patient sera (diluted 1 : 20) or EDTA‐blood (diluted 1 : 10) in incubation buffer (20 mM Tris HCl, 150 mM NaCl, 0·001% Azide, 0·1% BSA, 0·15% Tween‐20, pH 8·0) were incubated at 4 °C overnight in 96‐well microtiter plates.…”

Section: Methodsmentioning

confidence: 99%

“…The common techniques used for detection of onconeural antibodies are immunhistochemistry and immune blots with neuronal extracts or recombinant proteins [10]. We have recently employed a very sensitive immunoprecipitation technique for the detection of Hu antibodies [8,11]. The aim of this study was to apply the same immunoprecipitation technique to examine the prevalence of Yo antibodies in a large cohort of patients with ovarian or breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique

Monstad¹,

Storstein²,

Dørum

et al. 2006

Clinical and Experimental Immunology

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SummaryOnconeural antibodies are found in patients with cancer and are associated with paraneoplastic neurological syndromes (PNS). The objective of the present study was to assess the frequency of Yo antibodies in ovarian and breast cancer using a sensitive immunoprecipitation technique, and to look for any association of Yo antibodies with neurological symptoms and prognostic factors. A multiwell adapted fluid-phase immunoassay using radiolabelled recombinant cerebellar degeneration related protein (

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“…CDR1 cDNA was PCR amplified from the vector pCR-4 TOPO (ATCC) into a pET-100/D-TOPO vector (Thermo Fisher). ITT and IP were performed as previously described [ 28 - 32 ]. In brief ITT was performed using the TNT coupled reticulocyte lysate system (L4610, Promega) to produce [ 35 S]-methionine-labeled CDR1 protein by adding [ 35 S]-methionine (# NEG709A, PerkinElmer) to the reaction.…”

Section: Methodsmentioning

confidence: 99%

Expression of the onconeural protein CDR1 in cerebellum and ovarian cancer

et al. 2018

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Cerebellar degeneration related protein 1 (CDR1) is expressed in the cerebellum, and CDR1 antibodies have been associated with paraneoplastic cerebellar degeneration (PCD). In this study, we examined CDR1 expression in cerebellum and in ovarian and breast tumors, as well as the intracellular localization of CDR1 in cancer cells in culture. CDR1 was strongly expressed in the cytosol and dendrites of Purkinje cells and in interneurons of the molecular layer in cerebellum. CDR1 was also present in ovarian and breast tumors, as well as in ovarian and breast cancer cell lines, but was not present in normal breast or ovarian tissue. In cells overexpressing CDR1, CDR1 localized close to the plasma membrane in a polarized pattern at one edge. CDR1 was strongly expressed on the outer surface, apparently in filopodias or lamellipodias, in cells endogenously expressing CDR1. Overexpression of CDR1 showed a 37 and a 45 kDa band in western blot. The 37-kDa isoform was present in 16 ovarian cancer lysates, while the 45-kDa isoform was only found in three ovarian cancer patients. The presence of CDR1 in ovarian cancer was not associated with PCD. CDR1 antibodies were only found in serum from one patient with PCD and ovarian tumor with metastases. Therefore, CDR1 is probably not a marker for PCD. However, CDR1 may be associated with cell migration and differentiation.

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Paraneoplastic antibodies against HuD detected by a sensitive radiobinding assay

Cited by 15 publications

References 23 publications

Pyridoxal phosphatase is a novel cancer autoantigen in the central nervous system

Pyridoxal phosphatase is a novel cancer autoantigen in the central nervous system

Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique

Expression of the onconeural protein CDR1 in cerebellum and ovarian cancer

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