Behçet üveitinin immünopatogenezi ve IFN-α-2A tedavisine karşı immünyanıt

This study was conducted to investigate a) The immunopathogenesis of BD and BD Uveitis and b) the effect of interferon alfa-2a, on adaptive and innate immunity in patients with Behçet uveitis. For the adaptive immune responses, peripheral blood regulatory T Cells and TH17 cells were analyzed. For the innate immune responses, mRNA expression of TLRs 2, 3, 4, 8 and 9 on monocytes were analyzed. Nineteen patients with active Behçet uveitis who were refractory to conventional immunomodulatory therapy and were administered interferon alfa-2a; and age- and sex-matched healthy control subjects were consecutively enrolled from August 2016 to September 2017. Peripheral blood from patients was collected before treatment and after angiographic remission was achieved with interferon alfa-2a. Treg and TH17 percentages were determined as CD3+CD4+FoxP3+ and CD3+CD4+IL17A+ (after in vitro stimulation) respectively by flow-cytometry. TH17 RORɣT mRNA expression was verified by real-time PCR (RT PCR). Cytokines released from Treg and TH17 cells were detected by ELISA in culture supernatants. RT PCR was used to measure mRNA levels of TLRs 2, 3, 4, 8 and 9 from monocytes. R Statistical Software v.3.5.1 was used for statistics and Mann-Whitney U and Wilcoxon tests were used for analyses. Treg and TH17 percentages and TH17 RORɣT mRNA expression were found significantly elevated in BU patients. Patients had significantly lower Treg IL-10 concentration than controls. IL-17A, IL-6, IL-21, IL-22, IL-23, IFN-ɣ, and TNF-α concentrations from Th17 Cells were found to be significantly higher in patients than in controls. All TLR expressions were found significantly elevated in monocytes of BU patients. Interferon alfa-2a (median total dose: 330 million international units, median duration: 5 months) led to remission in BU patients. A significant reversal of Treg and TH17 percentage, TH17 RORɣT mRNA expression, Treg and TH17 cytokine release, and TLR expressions from monocytes were observed in BU patients after interferon therapy. Despite a paradoxical increase in Treg population, impaired IL-10 production suggests Treg dysfunction in patients with active BU. Interferon alfa-2a restored Treg functions, induces IL-10 production from Tregs, suppresses TH17s and downregulates TLR expression in monocytes.