Anti-Enolase-α Autoantibodies in Cancer-Associated Retinopathy: Epitope Mapping and Cytotoxicity on Retinal Cells

• Published in: Journal of autoimmunity Vol. 11; no. 6; pp. 671 - 677
• Main Authors: Adamus, G, Amundson, D, Seigel, G.M, Machnicki, M
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01.12.1998; Elsevier
• Subjects: Animals; apoptosis; Apoptosis - drug effects; Apoptosis - immunology; Autoantibodies - blood; Autoantibodies - immunology; Autoantibodies - pharmacology; Binding Sites; Biological and medical sciences; CAR; Cell Survival - drug effects; Cell Survival - physiology; Cytotoxicity, Immunologic; Epitope Mapping; Host-tumor relations. Immunology. Biological markers; Humans; Medical sciences; Neoplasms - blood; Neoplasms - complications; Neoplasms - immunology; paraneoplastic syndrome; Paraneoplastic Syndromes - blood; Paraneoplastic Syndromes - immunology; peptide; Phosphopyruvate Hydratase - immunology; Rats; retina; Retina - cytology; Retina - drug effects; Retina - immunology; Retinal Diseases - blood; Retinal Diseases - etiology; Retinal Diseases - immunology; Tumors; apoptosis; peptide; CAR; retina; paraneoplastic syndrome; Autoimmunity; Human; Immunopathology; Retinopathy; Antigenic determinant; Enzyme; Antibody; Pathogenesis; Autoantibody; Cytotoxicity; Retina; Lyases; Malignant tumor; In vitro; Eye disease; Specificity; Complication; Paraneoplastic syndrome; Carbon-oxygen lyases; Phosphopyruvate hydratase; Hydro-lyases; Apoptosis
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1998.0239

Patients with cancer-associated retinopathy syndrome (CAR), a progressive blinding disease related to retinal degeneration and systemic tumor outside the eye, develop autoantibodies against α-enolase. A small percentage of healthy subjects without evident tumor or visual symptoms also possess autoantibody against enolase. In these studies we examined the fine specificity of anti-enolase antibodies derived from patients with CAR and healthy individuals, using synthetic peptides covering the entire sequence of human α-enolase. Epitope mapping revealed that three binding regions of enolase within the residues 31–38 (FRAAVPSG), 176–183 (ANFREAMR), and 421–428 (AKFAGRNF) were common for all autoantibodies tested. However, pathogenic sera recognized an additional unique region, the sequence 56–63 (RYMGKGVS). There were also differences inin vitrocytotoxic activities on E1A.NR3 retinal cells and cell-death promoting activities between anti-enolase antibodies of healthy and CAR affected individuals. These studies showed that anti-enolase antibodies from patients with CAR were able to induce apoptotic cell death in E1A.NR3 retinal cells and provided a potential mechanism for retinal degeneration in humans.