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Masaru Takeuchi, Yoshihiko Usui, Yoko Okunuki, Lina Zhang, Juan Ma, Naoyuki Yamakawa, Takaaki Hattori, Takeshi Kezuka, Jun-ichi Sakai, Hiroshi Goto; Immune Responses to Interphotoreceptor Retinoid-Binding Protein and S-Antigen in Behçet's Patients with Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(6):3067-3075. doi: 10.1167/iovs.09-4313.
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Immune responses to retina-specific autoantigens, including S antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP), have been suggested to be involved in the pathogenesis of human uveitis, including Behçet's disease (BD). In this study, the authors examined whether immune responses to IRBP and S-Ag in BD patients can be characterized by cytokine production profiles.
Peripheral blood mononuclear cells (PBMCs) were collected from BD patients with uveitis and healthy controls, and each sample was cultured with IRBP, S-Ag, or purified protein derivative (PPD). At the end of culture, IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α concentrations in supernatants were measured.
PBMCs from BD patients and healthy controls produced IL-6, IL-10, IL-17, IFN-γ, and TNF-α on stimulation with IRBP or S-Ag, as well as PPD stimulation, immunity against which was acquired by Bacille Calmette-Guérin immunization. IL-17 and IFN-γ production was significantly higher when PBMCs were stimulated with IRBP than with S-Ag, whereas the reverse was observed for IL-6 production. IRBP-stimulated IL-6, IFN-γ, and IL-17 production was higher in BD patients than in healthy controls, though IL-10 production was not different between them. In particular, IRBP-stimulated IFN-γ production was significantly higher in BD patients with active uveitis than in BD patients with uveitis in remission.
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 in BD.
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