Identification and Functional Validation of Novel Autoantigens in Equine Uveitis

• Published in: Molecular & cellular proteomics 2006-08, Vol.5 (8), p.1462-1470
• Main Authors: Deeg, Cornelia A, Pompetzki, Dirk, Raith, Albert J, Hauck, Stefanie M, Amann, Barbara, Suppmann, Sabine, Goebel, Thomas W F, Olazabal, Ursula, Gerhards, Hartmut, Reese, Sven, Stangassinger, Manfred, Kaspers, Bernd, Ueffing, Marius
• Format: Article
• Language: English
• Subjects: Animals; Autoantigens - immunology; Autoantigens - metabolism; B-Lymphocytes - immunology; Carrier Proteins - immunology; Carrier Proteins - metabolism; Electrophoresis, Gel, Two-Dimensional; Eye Proteins - immunology; Eye Proteins - metabolism; Horse Diseases - immunology; Horse Diseases - pathology; Horses; Immunoglobulin G - metabolism; Protein Binding; Proteome - immunology; Proteome - metabolism; Rats; Rats, Inbred Lew; Retina - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; T-Lymphocytes - immunology; Uveitis - immunology; Uveitis - pathology; Uveitis - veterinary
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.M500352-MCP200

The development, progression, and recurrence of autoimmune diseases are frequently driven by a group of participatory autoantigens. We identified and characterized novel autoantigens by analyzing the autoantibody binding pattern from horses affected by spontaneous equine recurrent uveitis to the retinal proteome. Cellular retinaldehyde-binding protein (cRALBP) had not been described previously as autoantigen, but subsequent characterization in equine recurrent uveitis horses revealed B and T cell autoreactivity to this protein and established a link to epitope spreading. We further immunized healthy rats and horses with cRALBP and observed uveitis in both species with typical tissue lesions at cRALBP expression sites. The autoantibody profiling outlined here could be used in various autoimmune diseases to detect autoantigens involved in the dynamic spreading cascade or serve as predictive markers.