Anti-enolase-alpha autoantibodies in cancer-associated retinopathy: epitope mapping and cytotoxicity on retinal cells.
Patients with cancer-associated retinopathy syndrome (CAR), a progressive blinding disease related to retinal degeneration and systemic tumor outside the eye, develop autoantibodies against alpha-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 alpha-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 in in vitro cytotoxic 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.
Adamus
G
G
Neurological Sciences Institute, Oregon Health Sciences University, 1120 NW 20th Ave, Portland, OR, USA.
Amundson
D
D
Seigel
G M
GM
Machnicki
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000276:immunology; D010257:Paraneoplastic Syndromes / Q000097:blood / Q000276:immunology*; D010751:Phosphopyruvate Hydratase / Q000276:immunology*; D051381:Rats; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D012164:Retinal Diseases / Q000097:blood / Q000209:etiology / Q000276:immunology*
D001323:Autoantibodies; D010751:Phosphopyruvate Hydratase