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Immune responses to retinal autoantigens and peptides in equine recurrent uveitis.

Abstract: To test the hypothesis that autoimmune mechanisms are involved in horses in which equine recurrent uveitis (ERU) develops spontaneously. Methods: Material obtained from horses treated for spontaneous disease by therapeutic routine vitrectomy was analyzed for total IgG content and IgG specific for S-Antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP). The cellular infiltrate of the vitreous was analyzed by differential counts of cytospin preparations and flow cytometry using equine lymphocyte-specific antibodies. Antigen-specific proliferation assays were performed comparing peripheral blood lymphocytes (PBLs) with vitreal lymphocytes by stimulation with S-Ag and several S-Ag- and IRBP-derived peptides. Results: The total IgG content of specimens from horses with ERU was very high with great variability among the investigated samples (11.5 +/- 8.0 mg). Autoantibodies to S-Ag or IRBP or both were found in 72% of vitreous specimens from horses with uveitis. The leukocyte infiltrates (up to 2 x 10(8) cells per sample) were dominated by lymphocytes (>90%) in most cases (22/32). Flow cytometry showed that more than 50% of these cells were CD4(+) T cells. In vitro stimulation of vitreal lymphocytes, but not of PBL, showed a strong proliferative response to peptides derived from S-Ag or IRBP in 9 of 12 patients. Conclusions: In the eyes of horses with ERU, IgG antibodies and autoreactive T cells specific for retinal antigens were detected. These results strongly support the hypothesis that ERU is an autoimmune-mediated disease and is highly similar to recurrent uveitis in humans in both clinical and immunologic parameters.
Publication Date: 2001-02-07 PubMed ID: 11157872
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study examines the possibility that autoimmune mechanisms play a role in equine recurrent uveitis (ERU), a common and serious eye disease in horses. By analyzing material from horses who have undergone therapeutic routine vitrectomy, researchers identified high levels of IgG antibodies and autoreactive T cells, specific to retinal antigens. The findings support the theory that ERU in horses may indeed result from autoimmune responses.

Autoimmunity Hypothesis in ERU

  • The researchers aimed to test the hypothesis that autoimmune mechanisms could be involved in cases where equine recurrent uveitis (ERU) occurs spontaneously.
  • ERU is a condition characterized by the recurring inflammation of the uveal tract in the horse’s eye, leading to severe visual impairment or blindness.
  • The autoimmune reaction hypothesized here involves the body’s immune system attacking its own cells – in this case, the cells of the horse’s eyes.

Research Methods

  • This research involved obtaining material from horses treated for spontaneous ERU by a procedure known as therapeutic routine vitrectomy.
  • The obtained material was analyzed for total IgG (immune globulin G) content and IgG specific for S-Antigen (S-Ag) and Interphotoreceptor Retinoid-Binding Protein (IRBP). These substances are all linked to immune responses.
  • The researchers also performed antigen-specific proliferation assays to compare the responses of peripheral blood lymphocytes (PBLs) with vitreal lymphocytes when stimulated with S-Ag and several S-Ag- and IRBP-derived peptides.

Results & Conclusions

  • The total IgG content of samples from horses with ERU was found to be very high and varied greatly between samples. Autoantibodies to S-Ag or IRBP, or both, were found in 72% of vitreous samples from horses with uveitis.
  • The leukocyte infiltrates were dominated by lymphocytes in most cases. The researchers also saw more than 50% of these cells were CD4(+) T cells.
  • Strong proliferative responses to peptides derived from S-Ag or IRBP were seen in the in vitro stimulation of vitreal lymphocytes, but not in the peripheral blood lymphocytes.
  • Overall, the study’s findings suggest that ERU in horses might be a disease mediated by the autoimmune system. The detected IgG antibodies and autoreactive T cells in the horse’s eyes strengthen this theory.
  • These findings also highlight the similarity of ERU in horses to recurrent uveitis in humans, both clinically and immunologically.

Cite This Article

APA
Deeg CA, Kaspers B, Gerhards H, Thurau SR, Wollanke B, Wildner G. (2001). Immune responses to retinal autoantigens and peptides in equine recurrent uveitis. Invest Ophthalmol Vis Sci, 42(2), 393-398.

Publication

ISSN: 0146-0404
NlmUniqueID: 7703701
Country: United States
Language: English
Volume: 42
Issue: 2
Pages: 393-398

Researcher Affiliations

Deeg, C A
  • Institute of Animal Physiology, Ludwig-Maximilians University, Munich, Germany. deeg@tiph.vetmed.uni-muenchen.de
Kaspers, B
    Gerhards, H
      Thurau, S R
        Wollanke, B
          Wildner, G

            MeSH Terms

            • Animals
            • Antibody Formation
            • Arrestin / immunology
            • Autoantibodies / analysis
            • Autoantigens / immunology
            • Autoimmune Diseases / immunology
            • Autoimmune Diseases / surgery
            • Autoimmune Diseases / veterinary
            • CD4-Positive T-Lymphocytes / immunology
            • Eye Proteins
            • Flow Cytometry / veterinary
            • Horse Diseases / immunology
            • Horse Diseases / surgery
            • Horses
            • Immunoglobulin G / analysis
            • Immunophenotyping / veterinary
            • Lymphocyte Activation
            • Peptide Fragments / immunology
            • Recurrence
            • Retina / immunology
            • Retinol-Binding Proteins / immunology
            • Uveitis / immunology
            • Uveitis / surgery
            • Uveitis / veterinary
            • Vitrectomy / veterinary
            • Vitreous Body / cytology
            • Vitreous Body / immunology

            Citations

            This article has been cited 24 times.
            1. Kirmse L, Thieme K, Doherr MG, Eule JC. Evaluation of Laboratory Techniques for the Diagnosis of Leptospira-Associated Equine Recurrent Uveitis (ERU) With Focus on the Goldmann-Witmer Coefficient. Vet Ophthalmol 2026 Jan;29(1):e70132.
              doi: 10.1111/vop.70132pubmed: 41518147google scholar: lookup
            2. Sprenzel CJ, Amann B, Deeg CA, Degroote RL. Glycan Signatures on Neutrophils in an Equine Model for Autoimmune Uveitis. Biomolecules 2025 Oct 12;15(10).
              doi: 10.3390/biom15101444pubmed: 41154673google scholar: lookup
            3. 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
            4. 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
            5. Rodríguez-Martínez L, Rodríguez-Fernández CA, Rodríguez Lemos O, de Domingo B, García Bru P, Mateos J, Fernández-Ferreiro A. Potential Prognostic Protein Biomarkers in Tears From Noninfectious Uveitis Patients Under Biologic Treatment as a Prelude to Personalized Medicine. Invest Ophthalmol Vis Sci 2024 Nov 4;65(13):29.
              doi: 10.1167/iovs.65.13.29pubmed: 39540857google scholar: lookup
            6. Söth R, Hoffmann ALC, Deeg CA. Enhanced ROS Production and Mitochondrial Metabolic Shifts in CD4(+) T Cells of an Autoimmune Uveitis Model. Int J Mol Sci 2024 Oct 26;25(21).
              doi: 10.3390/ijms252111513pubmed: 39519064google scholar: lookup
            7. 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
            8. 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
            9. Fingerhut L, Yücel L, Strutzberg-Minder K, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N. Ex Vivo and In Vitro Analysis Identify a Detrimental Impact of Neutrophil Extracellular Traps on Eye Structures in Equine Recurrent Uveitis. Front Immunol 2022;13:830871.
              doi: 10.3389/fimmu.2022.830871pubmed: 35251020google scholar: lookup
            10. 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).
            11. 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
            12. Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
              doi: 10.3389/fimmu.2020.609855pubmed: 33488614google scholar: lookup
            13. Fingerhut L, Ohnesorge B, von Borstel M, Schumski A, Strutzberg-Minder K, Mörgelin M, Deeg CA, Haagsman HP, Beineke A, von Köckritz-Blickwede M, de Buhr N. Neutrophil Extracellular Traps in the Pathogenesis of Equine Recurrent Uveitis (ERU). Cells 2019 Nov 27;8(12).
              doi: 10.3390/cells8121528pubmed: 31783639google scholar: lookup
            14. Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ, Borjesson DL. Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro. Vet Ophthalmol 2020 Jan;23(1):160-170.
              doi: 10.1111/vop.12704pubmed: 31441218google scholar: lookup
            15. Paschalis-Trela K, Cywińska A, Trela J, Czopowicz M, Kita J, Witkowski L. The prevalence of ocular diseases in polish Arabian horses. BMC Vet Res 2017 Nov 7;13(1):319.
              doi: 10.1186/s12917-017-1252-8pubmed: 29115950google scholar: lookup
            16. 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
            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. 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
            19. Neutzner RV, Jäger M, Friedburg C, Deeg CA, Lorenz B. [Blind spot enlargement syndrome in acute zonal occult outer retinopathy with detection of autoantibodies against the retinal antigens CRALBP and S-Ag]. Ophthalmologe 2011 Nov;108(11):1045-9.
              doi: 10.1007/s00347-011-2406-xpubmed: 21904838google 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. Hauck SM, Dietter J, Kramer RL, Hofmaier F, Zipplies JK, Amann B, Feuchtinger A, Deeg CA, Ueffing M. Deciphering membrane-associated molecular processes in target tissue of autoimmune uveitis by label-free quantitative mass spectrometry. Mol Cell Proteomics 2010 Oct;9(10):2292-305.
              doi: 10.1074/mcp.M110.001073pubmed: 20601722google scholar: lookup
            22. Garweg JG, de Kozak Y, Goldenberg B, Boehnke M. Anti-retinal autoantibodies in experimental ocular and systemic toxoplasmosis. Graefes Arch Clin Exp Ophthalmol 2010 Apr;248(4):573-84.
              doi: 10.1007/s00417-009-1242-zpubmed: 19956968google scholar: lookup
            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
            24. Verma A, Artiushin S, Matsunaga J, Haake DA, Timoney JF. LruA and LruB, novel lipoproteins of pathogenic Leptospira interrogans associated with equine recurrent uveitis. Infect Immun 2005 Nov;73(11):7259-66.