Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the tumor of a patient with cancer-associated retinopathy.
Recoverin is a member of the EF-hand family of calcium-binding proteins involved in the transduction of light by vertebrate photoreceptors. Recoverin also was identified as an autoantigen in the degenerative disease of the retina known as cancer-associated retinopathy (CAR), a paraneoplastic syndrome whereby immunological events lead to the degeneration of photoreceptors in some individuals with cancer. In this study, we demonstrate that recoverin is expressed in the lung tumor of a CAR patient but not in similar tumors obtained from individuals without the associated retinopathy. Recoverin was identified intially by Western blot analysis of the CAR patient's biopsy tissue by using anti-recoverin antibodies generated against different regions of the recoverin molecule. In addition, cultured cells from the biopsy tissue expressed recoverin, as demonstrated by reverse transcription-PCR using RNA extracted from the cells. The immunodominant region of recoverin also was determined in this study by a solid-phase immunoassay employing overlapping heptapeptides encompassing the entire recoverin sequence. Two linear stretches of amino acids (residues 64-70, Lys-Ala-Tyr-Ala-Gln-His-Val; and 48-52, Gln-Phe-Gln-Ser-Ile) made up the major determinants. One of the same regions of the recoverin molecule (residues 64-70) also was uniquely immunopathogenic, causing photoreceptor degeneration upon immunization of Lewis rats with the corresponding peptide. These data demonstrate that the neural antigen recoverin more than likely is responsible for the immunological events associated with vision loss in some patients with cancer. These data also establish CAR as one of the few autoimmune-mediated diseases for which the specific self-antigen is known.
Polans
A S
AS
R. S. Dow Neurological Sciences Institute, Legacy-Good Samaritan Hospital, Portland, OR 97209, USA.
Witkowska
D
D
Haley
T L
TL
Amundson
D
D
Baizer
L
L
Adamus
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000032:analysis* / Q000096:biosynthesis*; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D005136:Eye Proteins; D005260:Female; D005455:Fluorescent Antibody Technique; D051597:Hippocalcin; D006801:Humans; D008074:Lipoproteins; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010257:Paraneoplastic Syndromes / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew / Q000276:immunology; D051603:Recoverin; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012164:Retinal Diseases / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D000939:Epitopes; D005136:Eye Proteins; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; C496731:RCVRN protein, human; C496733:Rcvrn protein, rat; D051603:Recoverin; D051597:Hippocalcin