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Molecular & cellular proteomics : MCP2006; 5(8); 1462-1470; doi: 10.1074/mcp.M500352-MCP200

Identification and functional validation of novel autoantigens in equine uveitis.

Abstract: 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.
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Publication Date: 2006-05-11 PubMed ID: 16690753DOI: 10.1074/mcp.M500352-MCP200Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on discovering and testing the role of new autoantigens in equine recurrent uveitis, an autoimmune disease in horses, by examining the pattern of autoantibody binding to the retinal proteome. The study’s key finding was the identification of cellular retinaldehyde-binding protein (cRALBP) as an autoantigen and its impact on the progression of the disease.

Identification of Novel Autoantigens

  • The researchers started by analyzing the pattern of autoantibody binding to the retinal proteome from horses affected by equine recurrent uveitis. This disease, a common cause of blindness in horses, is marked by repeated inflammatory episodes targeting the uvea, a layer of the horse’s eye.
  • The goal was to identify new autoantigens, a group of substances that trigger an immune response, contributing to the development and progression of autoimmune diseases.

Characterization of cRALBP as an Autoantigen

  • The researchers discovered that Cellular Retinaldehyde-Binding Protein (cRALBP) had not been previously identified as an autoantigen.
  • Further analysis in horses with equine recurrent uveitis revealed B and T cell autoreactivity to this protein, establishing a link to a phenomenon termed ‘epitope spreading’.
  • ‘Epitope spreading’ refers to the diversification of an autoimmune response to multiple epitopes, regions of a protein that antibodies can recognize and bind to, following the initial disease-triggering immune response.

Functional Validation of cRALBP as an Autoantigen

  • The study didn’t stop at characterizing cRALBP as an autoantigen. The next step was to validate the role of this protein in causing uveitis.
  • To do this, researchers immunized healthy rats and horses with cRALBP, subsequently observing the development of uveitis in both species, with typical tissue lesions at sites expressing cRALBP.
  • This outcome thus validated the role of cRALBP as an autoantigen inducing uveitis.

Potential Applications of the Study

  • The profiling approach used in this study to identify and test autoantigens can be applied to various autoimmune diseases.
  • By identifying autoantigens participating in ‘epitope spreading’, this approach can help tracking the dynamic progression of autoimmune diseases, or even serve as markers to predict the disease.

Cite This Article

APA
Deeg CA, Pompetzki D, Raith AJ, Hauck SM, Amann B, Suppmann S, Goebel TW, Olazabal U, Gerhards H, Reese S, Stangassinger M, Kaspers B, Ueffing M. (2006). Identification and functional validation of novel autoantigens in equine uveitis. Mol Cell Proteomics, 5(8), 1462-1470. https://doi.org/10.1074/mcp.M500352-MCP200

Publication

Molecular & cellular proteomics : MCP
ISSN: 1535-9476
NlmUniqueID: 101125647
Country: United States
Language: English
Volume: 5
Issue: 8
Pages: 1462-1470

Researcher Affiliations

Deeg, Cornelia A
  • Institute of Animal Physiology, Ludwig Maximilians University (LMU) Munich, Veterinärstr. 13, D-80539 Munich, Germany.
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

                          MeSH Terms

                          • 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

                          Citations

                          This article has been cited 23 times.
                          1. Fleischer AB, Amann B, von Toerne C, Degroote RL, Schmalen A, Weißer T, Hauck SM, Deeg CA. Differential Expression of ARG1 and MRC2 in Retinal Müller Glial Cells During Autoimmune Uveitis. Biomolecules 2025 Feb 14;15(2).
                            doi: 10.3390/biom15020288pubmed: 40001591google scholar: lookup
                          2. Gerras J, Young K, Roberts D, Waldman G, Salmon JH, Gilger BC. Uveitis and blindness in a closed herd of Equidae following leptospiral infection. Front Vet Sci 2024;11:1504990.
                            doi: 10.3389/fvets.2024.1504990pubmed: 39834922google scholar: lookup
                          3. Chistyakov DV, Tiulina VV, Gancharova OS, Baksheeva VE, Goriainov SV, Shebardina NG, Ivlev VA, Komarov SV, Shevelyova MP, Tikhomirova NK, Philippov PP, Vasil'ev VG, Sergeeva MG, Permyakov SE, Iomdina EN, Tsvetkov PO, Senin II, Zernii EY. Targeting Oxidative Stress and Inflammation in the Eye: Insights from a New Model of Experimental Autoimmune Uveitis. Int J Mol Sci 2024 Nov 30;25(23).
                            doi: 10.3390/ijms252312910pubmed: 39684616google scholar: lookup
                          4. Degroote RL, Schmalen A, Hauck SM, Deeg CA. Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis. Biomedicines 2023 Dec 20;12(1).
                            doi: 10.3390/biomedicines12010019pubmed: 38275380google scholar: lookup
                          5. Hoffmann ALC, Hauck SM, Deeg CA, Degroote RL. Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro. Int J Mol Sci 2022 Aug 23;23(17).
                            doi: 10.3390/ijms23179555pubmed: 36076947google scholar: lookup
                          6. Wollanke B, Gerhards H, Ackermann K. Infectious Uveitis in Horses and New Insights in Its Leptospiral Biofilm-Related Pathogenesis. Microorganisms 2022 Feb 7;10(2).
                            doi: 10.3390/microorganisms10020387pubmed: 35208842google scholar: lookup
                          7. Barfüßer C, Wiedemann C, Hoffmann ALC, Hirmer S, Deeg CA. Altered Metabolic Phenotype of Immune Cells in a Spontaneous Autoimmune Uveitis Model. Front Immunol 2021;12:601619.
                            doi: 10.3389/fimmu.2021.601619pubmed: 34385998google scholar: lookup
                          8. Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
                            doi: 10.3389/fimmu.2020.609855pubmed: 33488614google scholar: lookup
                          9. Wiedemann C, Amann B, Degroote RL, Witte T, Deeg CA. Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses. Front Cell Dev Biol 2020;8:101.
                            doi: 10.3389/fcell.2020.00101pubmed: 32211402google scholar: lookup
                          10. Busch M, Wefelmeyer KL, Walscheid K, Rothaus K, Bauer D, Deeg CA, Degroote RL, Ackermann D, König S, Thanos S, Kasper M, Heiligenhaus A. Identification of Ocular Autoantigens Associated With Juvenile Idiopathic Arthritis-Associated Uveitis. Front Immunol 2019;10:1793.
                            doi: 10.3389/fimmu.2019.01793pubmed: 31447836google scholar: lookup
                          11. Sandmeyer LS, Bauer BS, Feng CX, Grahn BH. Equine recurrent uveitis in western Canadian prairie provinces: A retrospective study (2002-2015). Can Vet J 2017 Jul;58(7):717-722.
                            pubmed: 28698690
                          12. Simeonova GP, Krastev SZ, Simeonov RS. Immunological and pathological investigations in equine experimental uveitis. Vet Res Commun 2016 Dec;40(3-4):107-115.
                            doi: 10.1007/s11259-016-9659-4pubmed: 27344152google scholar: lookup
                          13. Deeg CA, Amann B, Lutz K, Hirmer S, Lutterberg K, Kremmer E, Hauck SM. Aquaporin 11, a regulator of water efflux at retinal Müller glial cell surface decreases concomitant with immune-mediated gliosis. J Neuroinflammation 2016 Apr 23;13(1):89.
                            doi: 10.1186/s12974-016-0554-2pubmed: 27107718google scholar: lookup
                          14. Uhl PB, Amann B, Hauck SM, Deeg CA. Novel localization of peripherin 2, the photoreceptor-specific retinal degeneration slow protein, in retinal pigment epithelium. Int J Mol Sci 2015 Jan 26;16(2):2678-92.
                            doi: 10.3390/ijms16022678pubmed: 25629227google scholar: lookup
                          15. Degroote RL, Hauck SM, Amann B, Hirmer S, Ueffing M, Deeg CA. Unraveling the equine lymphocyte proteome: differential septin 7 expression associates with immune cells in equine recurrent uveitis. PLoS One 2014;9(3):e91684.
                            doi: 10.1371/journal.pone.0091684pubmed: 24614191google scholar: lookup
                          16. Kulbrock M, Lehner S, Metzger J, Ohnesorge B, Distl O. A genome-wide association study identifies risk loci to equine recurrent uveitis in German warmblood horses. PLoS One 2013;8(8):e71619.
                            doi: 10.1371/journal.pone.0071619pubmed: 23977091google scholar: lookup
                          17. Swadzba ME, Hauck SM, Naim HY, Amann B, Deeg CA. Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis. PLoS One 2012;7(12):e50929.
                            doi: 10.1371/journal.pone.0050929pubmed: 23236410google scholar: lookup
                          18. Szober CM, Hauck SM, Euler KN, Fröhlich KJ, Alge-Priglinger C, Ueffing M, Deeg CA. Profound re-organization of cell surface proteome in equine retinal pigment epithelial cells in response to in vitro culturing. Int J Mol Sci 2012 Oct 31;13(11):14053-72.
                            doi: 10.3390/ijms131114053pubmed: 23203049google scholar: lookup
                          19. Deeg CA, Eberhardt C, Hofmaier F, Amann B, Hauck SM. Osteopontin and fibronectin levels are decreased in vitreous of autoimmune uveitis and retinal expression of both proteins indicates ECM re-modeling. PLoS One 2011;6(12):e27674.
                            doi: 10.1371/journal.pone.0027674pubmed: 22194789google scholar: lookup
                          20. Verma A, Kumar P, Babb K, Timoney JF, Stevenson B. Cross-reactivity of antibodies against leptospiral recurrent uveitis-associated proteins A and B (LruA and LruB) with eye proteins. PLoS Negl Trop Dis 2010 Aug 3;4(8):e778.
                            doi: 10.1371/journal.pntd.0000778pubmed: 20689825google scholar: lookup
                          21. Roelfstra L, Deeg CA, Hauck SM, Buse C, Membrez M, Betschart B, Pfister K. Protein expression profile of Gasterophilus intestinalis larvae causing horse gastric myiasis and characterization of horse immune reaction. Parasit Vectors 2009 Jan 8;2(1):6.
                            doi: 10.1186/1756-3305-2-6pubmed: 19133133google scholar: lookup
                          22. Okunuki Y, Usui Y, Kezuka T, Hattori T, Masuko K, Nakamura H, Yudoh K, Goto H, Usui M, Nishioka K, Kato T, Takeuchi M. Proteomic surveillance of retinal autoantigens in endogenous uveitis: implication of esterase D and brain-type creatine kinase as novel autoantigens. Mol Vis 2008 Jun 12;14:1094-104.
                            pubmed: 18552983
                          23. Deeg CA, Raith AJ, Amann B, Crabb JW, Thurau SR, Hauck SM, Ueffing M, Wildner G, Stangassinger M. CRALBP is a highly prevalent autoantigen for human autoimmune uveitis. Clin Dev Immunol 2007;2007:39245.
                            doi: 10.1155/2007/39245pubmed: 18317528google scholar: lookup
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