Inter- and intramolecular epitope spreading in equine recurrent uveitis.
Abstract: To test the hypothesis that inter- and intramolecular spreading to S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP)-derived epitopes occurs in a spontaneous model of recurrent uveitis in the horse. Methods: The immune response of eight horses with equine recurrent uveitis (ERU) was compared with that of five control horses with healthy eyes. Lymphocytes derived from peripheral blood (PBLs) were tested every 8 weeks for their reactivity against S-Ag and various S-Ag and IRBP-derived peptides for 12 to 39 months (median, 22 months). During uveitic episodes, additional blood samples were analyzed. Results: Intermolecular epitope spreading was detectable in all ERU cases during the study. Intramolecular spreading occurred in seven (of eight) horses with ERU. Fourteen relapses were analyzed during the observation period. Ten uveitic episodes were accompanied by neoreactivity to S-Ag or IRBP-derived peptides during the relapse. Shifts in the immune response profile were also detectable without any clinical signs of inflammation. Eye-healthy control horses were negative at all time points in the in vitro proliferation assays. Conclusions: Inter- and intramolecular spreading was detectable in a spontaneous model of recurrent uveitis. The shifts in immunoreactivity could account for the remitting-relapsing character of the disease.
Publication Date: 2006-01-25 PubMed ID: 16431964DOI: 10.1167/iovs.05-0789Google Scholar: Lookup
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- Journal Article
Summary
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The study sought to investigate the phenomenon of inter- and intramolecular epitope spreading in equine recurrent uveitis, a spontaneous horse model. Epitope spreading refers to the immune response diversifying to target multiple distinct parts of an antigen over time. The study finds that this phenomenon could be linked to the recurring nature of the disease.
Objective and Method
- The research was conducted with the objective of testing a hypothesis – that epitope spreading, both intermolecular (between different molecules) and intramolecular (within the same molecule), occurs in equine recurrent uveitis (ERU), an eye disease in horses. The antigens under scrutiny were S-Ag and IRBP-derived (interphotoreceptor retinoid binding protein).
- Eight horses diagnosed with ERU were compared with five control horses that were disease-free. The immune responses were evaluated by testing peripheral blood lymphocytes (PBLs) every 8 weeks over a period of 12 to 39 months. The reactivity against S-Ag and various derived peptides was measured. When the horses were experiencing active disease, additional blood samples were investigated.
Results and Findings
- As per the study outcomes, all ERU cases reflected the presence of intermolecular epitope spreading throughout the study period, and intramolecular spreading in seven out of eight ERU cases. This means that their immune responses diversified to target various segments of different molecules, as well as different sections within the same molecule.
- During the observation period, 14 uveitis relapses were analyzed. Ten of these episodes displayed new immune reactivity to either S-Ag or IRBP peptides at the time of relapse. Interestingly, shifts in immune response were also observed absent any clinical symptoms of inflammation.
- The control group which was comprised of horses with healthy eyes, did not exhibit any changes in their in vitro proliferation assays over the course of this study.
Conclusion
- This research concludes that in the spontaneous model of recurrent uveitis, epitope spreading does indeed occur: both inter- and intramolecular.
- The findings demonstrate shifts in immunoreactivity, which potentially contributes to the recurring characteristic of ERU. This fact may suggest new avenues for research into the mechanisms and treatment of this disease.
Cite This Article
APA
Deeg CA, Amann B, Raith AJ, Kaspers B.
(2006).
Inter- and intramolecular epitope spreading in equine recurrent uveitis.
Invest Ophthalmol Vis Sci, 47(2), 652-656.
https://doi.org/10.1167/iovs.05-0789 Publication
Researcher Affiliations
- Institute for Animal Physiology, Ludwig-Maximilians-University, Munich, Germany. deeg@tiph.vetmed.uni-muenchen.de
MeSH Terms
- Animals
- Arrestin / immunology
- Autoantibodies / immunology
- Autoantigens / immunology
- Epitopes / immunology
- Horse Diseases / immunology
- Horses
- Lymphocyte Activation / physiology
- Models, Animal
- Panuveitis / immunology
- Panuveitis / veterinary
- Peptide Fragments / immunology
- Recurrence
- Retinol-Binding Proteins / immunology
- T-Lymphocytes / immunology
- Uveitis, Anterior / immunology
- Uveitis, Anterior / veterinary
Citations
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