[The suppression of the experimental autoimmune uveoretinitis with retinal S antigens by intranasal tolerance induction].

OBJECTIVE: The aim was to investigate the suppression of rat experimental autoimmune uveoretinitis( EAU) by induced immune tolerance via intranasal administration of retinal S antigens. METHODS: The bovine S antigen was purified from bovine retina by salt precipitation and ionic exchange chromatography, the female Lewis rats were used to induce immune tolerance by intranasal administration with purified bovine retinal S antigens and then the rats were used to produce the EAU model by retinal S antigens challenge. The rate of EAU occurrence, the clinical and histological scores, the skin delayed-type hypersensitivity and lymphocyte proliferation stimulated by retinal S antigen and concanavalin A were recorded. The adjunct effect of cyclophosphamide on tolerance induction was observed. RESULTS: After intranasal administration of retinal S antigens, EAU was induced in two of eight ( 25% ) rats in tolerant group, sis of six (100%) rats in control group , the difference of EAU induction rate was significant in tolerant group compared with control (P = 0. 0097) . The average onset time in tolerant group were 16. 5 days, the control group was 10. 3 days, the difference was significant ( F = 26. 32, P = 0. 000; q = 9. 723, P <0. 01). The average clinical scores of EAU in tolerant group were 0. 89, the control group was 3. 94, the difference was significant( F = 12. 48 ,P = 0. 000; q = 7. 904, P < 0. 01 ). The average histological scores of EAU in tolerant group were 1. 21, the control group was 4. 12, the difference was significant( F = 11. 80, P = 0. 000; q = 7. 510,P <0. 01). The histological features in tolerant group were iris blood vessels slightly dilation, few exudates in anterior chamber and vitreous cavity; there were slighter retina swallow and the photoreceptors damages in the tolerant group. The skin delayed-type hypersensitivity and the proliferative responses of lymphocytes stimulated by S antigen and concanavalin A in tolerant group were slighter than that in the control group. Intraperitoneal injection of cyclophosphamide enhanced the effect of immune tolerance slightly. Only intraperitoneal injection of cyclophosphamide did not diminish the severity of the rat EAU. CONCLUSION: The intranasal induced tolerance by retinal S antigens can suppress effectively the prevalence of rat experimental autoimmune uveoretinitis induced by retinal S antigens.

Imunidade celular ao antígeno S empacientes com uveíte endógena / Cellular immune responses to S-antigen in endogenous uveitis

A auto-imunidade retiniana desempenha um papel na etiopatogenia de várias uveítes endógenas. Estudos experimentais e ensaios clínicos têm demonstrado a importância de antígenos retinianos, como o antígeno S (AgS), näo somente na patogenia mas também na elaboraçäo de estratégias de imunoterapia. O presente trabalho visa analisar o perfil da imunidade celular in vitro ao AgS e a dois de seus peptídeos relevantes, denominados M e G, em uma populaçäo brasileira com diagnóstico de uveíte por doença de Behçet (DB) (n=19), doença de Vogt-koyanagi-Harada (DVKH) (n=27) e vasculite da retina (n=5) acompanhados no serviço de uveíte do Hospital das Clínicas da Faculdade de Medicina da USP. Pacientes com DB sem uveíte (n=17) e 16 controles normais foram também analisados ..

Treatment of uveitis by oral administration of retinal antigens: results of a phase I/II randomized masked trial.

PURPOSE: To evaluate the effect and safety of the oral administration of retinal antigens as a treatment of ocular inflammation. METHODS: In a phase I/II randomized masked trial, patients with endogenous uveitis who were dependent on immunosuppressive agents were randomly assigned to receive either retinal S antigen alone (10 patients), retinal S antigen and a mixture of soluble retinal antigens (10 patients), a mixture of soluble retinal antigens alone (10 patients), or placebo (15 patients). An attempt was then made to taper patients completely off their standard immunosuppressive therapy over an 8 week period. The primary study endpoint was time to ocular inflammatory attack. The secondary study endpoint was the ability to taper patients completely off their immunosuppressive or cytotoxic medication within 8 weeks. RESULTS: Time to development of the main study endpoint was not statistically significantly different for any of the four treatment groups. However, the group receiving the purified S antigen alone appeared to be tapered off their immunosuppressive medication more successfully compared with patients given placebo (P = .08), whereas all the other groups appeared to do worse than did those receiving placebo. No toxic effects attributable to any treatment were observed. CONCLUSIONS: This phase I/II study is the first to test the use of orally administered S antigen in the treatment of uveitis. Although not statistically significant, patients given S antigen were more likely to be tapered off their chronically administered systemic immunosuppressive therapy than were the other groups tested.

Suppression of experimental autoimmune uveitis in Lewis rats by oral administration of recombinant Escherichia coli expressing retinal S-antigen.

Experimental autoimmune uveitis (EAU) is an organ-specific T-lymphocyte-mediated autoimmune disease which serves as a model for several human ocular inflammations of an apparently autoimmune nature. S-antigen, a photoreceptor cell protein, is highly efficient in inducing EAU showing severe inflammation of the uveal tract and retina of the eye. We have demonstrated previously that recombinant Escherichia coli expressing retinal S-antigen induces EAU in Lewis rats. The oral administration of S-antigen prior to the uveitopathogenic challenge results in significant suppression of the disease and of the cellular responses. We examined the effect of oral administration of E. coli expressing retinal S-antigen on the development of EAU induced with native S-antigen in Lewis rats. Feeding rats with 1 mg of bacteria on Days 7, 5, 3, 2 and 1 prior to immunization with 50 micrograms of retinal S-antigen caused a significant suppression of the disease. Moderate suppression was found in animals fed 0.5 and 0.25 mg of recombinant bacteria. Oral feeding of 1 mg of JM105 transfected with plasmid alone had no significant effect on the subsequent induction of EAU by S-antigen. Feeding recombinant E. coli expressing retinal S-antigen before immunization significantly decreased the proliferative response of lymphocytes to native S-antigen in vitro. Our results indicate that recombinant microorganism-expressing autoantigen administered orally induces suppression of specific autoimmune disease as well as cellular response to particular autoantigen.