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M. Takeuchi, Y. Usui, Y. Okunuki, L. Zhang, J. Ma, N. Yamakawa, T. Hattori, T. Kezuka, H. Goto; Immune Responses to Interphotoreceptor Retinoid-Binding Protein and S-Antigen in Behçet's Patients With Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3775.
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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 33 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 IRBP, S-Ag, or purified protein derivative (PPD). At the end of culture, supernatants were collected, and IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF-α 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 controls produced IL-6, IL-10, IL-17, IFN-γ and TNF-α upon stimulation with IRBP or S-Ag, and their amounts were comparable with those by PPD stimulation. Productions of IL-17 and IFN-γ were significantly higher when PBMCs were stimulated with IRBP than with S-Ag, while the reverse was observed for IL-6 production. IRBP-stimulated IL-6, IFN-γ and IL-17 productions were higher in BD patients than in healthy controls, but IL-10 production was not different between two groups. Especially, IRBP-stimulated IFN-γ production was significantly higher in BD patients with active uveitis compared to BD patients with uveitis in remission. When stimulated with PPD, these cytokine productions were higher in BD patients than in healthy controls, however there were no significant differences between them.
Th1, Th2, and Th17-medicated immune responses to both IRBP and S-Ag were observed even in PBMCs of healthy controls. However, the present results suggested that retinal autoantigen-stimulated IL-6, IL-17, and especially IFN-γ production would be involved in the development of uveitis of BD.CR: None
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