Cloning of a Brain Protein Identified by Autoantibodies from a Patient with Paraneoplastic Cerebellar Degeneration

• Published in: Proceedings of the National Academy of Sciences - PNAS 1987-07, Vol.84 (13), p.4552-4556
• Main Authors: Dropcho, Edward J., Chen, Yao-Tseng, Posner, Jerome B., Old, Lloyd J.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - complications; Adenocarcinoma - immunology; Amino Acid Sequence; Amino acids; Antibodies; Antibodies, Neoplasm - immunology; autoantibodies; Autoantibodies - immunology; Autoantigens - genetics; Autoantigens - immunology; Autoimmune Diseases - etiology; Autoimmune Diseases - immunology; Base Sequence; Biological and medical sciences; Biotechnology; brain; cDNA; Cell lines; cerebellar degeneration-related protein; Cerebellar Diseases - immunology; Cerebellum; Cloning, Molecular; Complementary DNA; DNA; DNA - genetics; DNA, Recombinant; Fundamental and applied biological sciences. Psychology; gene expression; Generally accepted auditing standards; Genes; Genetic engineering; Genetic technics; Humans; immunoglobulin G; Immunoglobulin G - immunology; man; Methods. Procedures. Technologies; Molecular cloning; mRNA; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Neoplasms - genetics; Neoplasms, Unknown Primary - complications; Neoplasms, Unknown Primary - immunology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - immunology; nucleotide sequence; paraneoplastic cerebellar degeneration; Paraneoplastic Syndromes - immunology; Purkinje Cells - immunology; recognition; Renal cell carcinoma; RNA; Tandem repeat sequences
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.13.4552

Autoantibodies directed against neuronal proteins have been identified in some patients with paraneoplastic cerebellar degeneration. To identify the molecular targets for these autoantibodies, we constructed a λ gt11 cDNA expression library from human cerebellum and screened the library with IgG from a patient with paraneoplastic cerebellar degeneration. A single clone, pCDR2, produced a fusion protein that reacted strongly with the patient's IgG. The isolated pCDR2 clone was used to identify six overlapping cDNA clones. Sequencing of the pCDR clones revealed a distinctive pattern consisting of a unit of 18 nucleotides (6 amino acids) repeated in tandem along the entire cDNA sequence. This sequence is unlike any previously described eukaryotic gene. Southern blot analysis was consistent with single-copy representation of the CDR (cerebellar degeneration-related) gene in the human and mouse genome. RNA blotting studies with normal tissues showed expression of the CDR gene to be largely restricted to brain. Expression of the CDR message was also noted in cell lines derived from cancers of neuroectodermal, kidney, and lung origin.