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M. Takeuchi, Y. Usui, T. Hattori, Y. Okunuki, L. Zhang, N. Yamakawa, J. Ma, J.-I. Sakai, T. Kezuka, H. Goto; Immune Responses to Retina-Specific Antigens in Behçet's Patients With Uveitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6144.
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The role of autoimmune mechanisms in the pathogenesis of some human uveitic conditions has been suggested by in vitro studies demonstrating that lymphocytes from uveitic patients respond against retina-specific antigens that are uveitogenic in animals. It has also been shown that the majority of patients with uveitis associated with Behçet's disease (BD) respond to S antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP), while some healthy subjects also respond to these antigens. In this study, we evaluated their immune responses to retina-specific antigens by examining the profile of cytokine production.
Peripheral blood mononuclear cells (PBMCs) were collected from 32 BD patients with uveitis and 23 healthy subjects, and each sample was cultured for 48 hrs with 0, 1, 5 or 10 µg/ml of S-Ag or IRBP purified from swine retinae. At the end of culture, supernatants were collected, and IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF- concentrations were measured by a cytometric bead array (CBA) kit using FACS and IL-17 concentration was determined by ELISA.
PBMCs from both BD patients and healthy subjects produced IL-6, IL-10, IL-17, IFN-γ and TNF- upon stimulation with S-Ag or IRBP in a dose-dependent manner, but did not produce IL-2 or IL-4. Both S-Ag- and IRBP-stimulated IL-6, IL-17, IFN-γ and TNF- productions were higher in BD patients than in healthy subjects but IL-10 production was not different between two groups. Especially, IRBP-stimulated IFN-γ production as well as S-Ag- and IRBP-stimulated IL-6 production were significantly higher in BD patients compared with healthy subjects. Interestingly, IFN-γ production was significantly higher when stimulated by IRBP than by S-Ag, whereas IL-6 production was significantly higher when stimulated by S-Ag than by IRBP.
These results indicate that both S-Ag and IRBP act as retinal autoantigens, and suggest that IFN-γ-mediated immune response induced by IRBP and IL-6-mediated immune response induced preferably by S-Ag may play critical roles in the occurrence of ocular inflammation in Behçet's disease.
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