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Masaru Takeuchi, Yoko Karasawa, Kohzou Harimoto, Yutaka Sakurai, Tomohito Sato, Rachel R. Caspi, Masataka Ito; Immune responses of Behçet’s disease patients with or without recurrent uveitis after infliximab treatment. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1891.
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© ARVO (1962-2015); The Authors (2016-present)
Infliximab is a chimeric IgG1 monoclonal antibody that blocks binding of TNFα to its receptor, and various studies have shown remarkably beneficial effects of infliximab in the treatment of Behçet’s disease (BD)-associated uveitis. However, recurrent uveitis was observed in some BD patients after initiation of infliximab treatment. It has been found that peripheral blood mononuclear cells (PBMCs) produce proinflammatory cytokines, and Th1-, Th2-, and Th17-related cytokines when stimulated with IRBP. In this study, we examined the quantitative changes of proinflammatory cytokines, and Th1-, Th2-, and Th17-related cytokines produced by PBMCs from BD patients with uveitis before and after treatment with infliximab when stimulated with retinal self-antigen. Furthermore, we compared cytokine production between BD patients with recurrent uveitis during infliximab treatment and those in whom recurrent uveitis was not observed after initiation of infliximab treatment.
PBMCs were obtained from 4 BD patients with recurrent uveitis (BD-recurrent uveitis group) and 4 BD patients with remitted uveitis (BD-remitted uveitis group) after initiation of infliximab before and 1 week after infliximab infusion. PBMCs were cultured in vitro with various concentrations of IRBP, and levels of IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-25, IL-33, IL-31, soluble CD40 ligand (sCD40L), IFN-γ, and TNFα in cultures were measured.
Levels of IL-1β, IL-4, IL-17A, IL-17F, IL-21, IL-22, IL-31, IFN-γ, sCD40L, and TNFα were higher, with a significant difference for IL-17F in BD-recurrent uveitis group than in BD-remitted uveitis group. Only the level of IL-10 was higher in the remission group than in recurrence group. After infliximab infusion, levels of cytokines except for IL-4, IL-22, and sCD40L were not apparently reduced in BD-recurrent uveitis group. On the other hand, levels of IL-6, IL-10, IL-17F, IL-22, IL-31, IFN-γ, and TNFα were lower, with significant differences for IL-17F, IL-22, and sCD40L, in BD-remitted uveitis group.
Th-related cytokines by PBMCs upon IRBP stimulation were suppressed after infliximab infusion preferentially in BD patients without recurrent uveitis. Measurement of these cytokines by IRBP-stimulated PBMCs would be a clue to evaluate quantitatively the efficacy of infliximab treatment for uveitis in BD patients.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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