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Cerebellar degeneration-related antigen: a highly conserved neuroectodermal marker mapped to chromosomes X in human and mouse.

ABSTRACT: Cerebellar degeneration-related antigen (designated CDR34) was previously cloned by antibody screening of a cDNA library and was shown to be one of the target molecules recognized by autoantibodies in patients with paraneoplastic cerebellar degeneration. This molecule is distinctive in that it contains a tandem hexapeptide repetitive structure, presumably the basis for its high immunogenicity. In this study, we cloned the human CDR34 gene and proved that the entire repetitive sequence is encoded by a single exon without introns. We also showed that the nucleotide repeats are preserved only in the protein-coding sequences, suggesting evolutionary constraint in this region of the gene. Corresponding mouse cDNA clones were also isolated, which encoded a larger molecule with very similar hexapeptide repeating units. Comparison of the human and mouse repeats revealed a highly conserved Glu-Asp core in each unit, implicating the functional significance of this motif. Chromosomal mapping by somatic cell hybrid analysis mapped CDR34 to both human and mouse chromosomes X, and in situ hybridization further assigned CDR34 to human Xq24-q27.

SUBMITTER: Chen YT

PROVIDER: S-EPMC53837 | biostudies-other | 1990 Apr

REPOSITORIES: biostudies-other

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Cerebellar degeneration-related antigen: a highly conserved neuroectodermal marker mapped to chromosomes X in human and mouse.

Chen Y T YT Rettig W J WJ Yenamandra A K AK Kozak C A CA Chaganti R S RS Posner J B JB Old L J LJ

Proceedings of the National Academy of Sciences of the United States of America 19900401 8

Cerebellar degeneration-related antigen (designated CDR34) was previously cloned by antibody screening of a cDNA library and was shown to be one of the target molecules recognized by autoantibodies in patients with paraneoplastic cerebellar degeneration. This molecule is distinctive in that it contains a tandem hexapeptide repetitive structure, presumably the basis for its high immunogenicity. In this study, we cloned the human CDR34 gene and proved that the entire repetitive sequence is encoded ...[more]

PMID: 2326268

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Project description:ObjectiveTo report on a novel neuronal target antigen in 3 patients with autoimmune cerebellar degeneration.MethodsThree patients with subacute to chronic cerebellar ataxia and controls underwent detailed clinical and neuropsychological assessment together with quantitative high-resolution structural MRI. Sera and CSF were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IFA) and immunoblot. Immunoprecipitation with lysates of hippocampus and cerebellum combined with mass spectrometric analysis was used to identify the autoantigen, which was verified by recombinant expression in HEK293 cells and use in several immunoassays. Multiparameter flow cytometry was performed on peripheral blood and CSF, and peripheral blood was subjected to T-cell receptor spectratyping.ResultsPatients presented with a subacute to chronic cerebellar and brainstem syndrome. MRI was consistent with cortical and cerebellar gray matter atrophy associated with subsequent neuroaxonal degeneration. IFA screening revealed strong immunoglobulin G1 reactivity in sera and CSF with hippocampal and cerebellar molecular and granular layers, but not with a panel of 30 recombinantly expressed established neural autoantigens. Neurochondrin was subsequently identified as the target antigen, verified by IFA and immunoblot with HEK293 cells expressing human neurochondrin as well as the ability of recombinant neurochondrin to neutralize the autoantibodies' tissue reaction. Immune phenotyping revealed intrathecal accumulation and activation of B and T cells during the acute but not chronic phase of the disease. T-cell receptor spectratyping suggested an antigen-specific T-cell response accompanying the formation of antineurochondrin autoantibodies. No such neurochondrin reactivity was found in control cohorts of various neural autoantibody-associated neurologic syndromes, relapsing-remitting multiple sclerosis, cerebellar type of multiple system atrophy, hereditary cerebellar ataxias, other neurologic disorders, or healthy donors.ConclusionNeurochondrin is a neuronal target antigen in autoimmune cerebellar degeneration.

Dataset Information

Cerebellar degeneration-related antigen: a highly conserved neuroectodermal marker mapped to chromosomes X in human and mouse.

Publications

Cerebellar degeneration-related antigen: a highly conserved neuroectodermal marker mapped to chromosomes X in human and mouse.

Similar Datasets

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