背景:银屑病是一种T细胞介导的慢性炎症性皮肤病。提示Th1、Th17和Th22细胞参与了银屑病的发病机制。
目的:为了确定是否使用抗肿瘤坏死因子拮抗剂治疗,阿达木单抗,诱导Th1,Th17和Th22途径的显着调节,并将细胞活性与临床反应相关联。
方法:本研究纳入了21例接受阿达木单抗治疗的中重度银屑病患者,和10名健康对照受试者。在基线和第12周收集血液样品。流式细胞术用于分析循环Th1,Th17和Th22细胞的频率。实时聚合酶链反应用于分析T-bet(Th1相关)的表达,类维生素A酸受体相关孤儿受体γt(RORγt,Th17相关)和芳烃受体(AHR,Th22相关)。酶联免疫吸附试验用于分析血清IFN-γ的水平,IL-17、IL-22、IL-6和肿瘤坏死因子-α(TNF-α)。
结果:在基线时,与健康对照组相比,银屑病患者中Th1,Th17和Th22细胞的频率更高。转录因子T-bet的表达,RORγt和AHR,和IFN-γ的血清水平,与健康对照组相比,银屑病患者的IL-17,IL-22,IL-6和TNF-α较高。阿达木单抗治疗后,Th1,Th17和Th22细胞的频率显着下降,并伴随其相关转录因子和细胞因子水平的降低。
结论:结果表明,抗肿瘤坏死因子拮抗剂,阿达木单抗,破坏Th1、Th17和Th22通路,导致银屑病的临床改善。
BACKGROUND: Psoriasis is a T-cell-mediated chronic inflammatory dermatosis. Th1, Th17 and Th22 cells are suggested to contribute to the pathogenesis of psoriasis.
OBJECTIVE: To determine whether treatment with the anti-tumor-necrosis-factor antagonist, adalimumab, induces significant modulation of the Th1, Th17 and Th22 pathways, and correlates cellular activity with clinical response.
METHODS: This study included 21 patients with moderate-to-severe psoriasis who were treated with adalimumab, and 10 healthy control subjects. Blood samples were collected at baseline and at week 12. Flow cytometry was used to analyze the frequency of circulating Th1, Th17 and Th22 cells. Real-time polymerase chain reaction was used to analyze the expression of T-bet (Th1-related), retinoid-acid receptor-related orphan receptor gamma t (RORγt, Th17-related) and aryl hydrocarbon receptor (AHR, Th22-related). An enzyme-linked immunosorbent assay was used to analyze the serum levels of IFN-γ, IL-17, IL-22, IL-6 and tumor necrosis factor-α (TNF-α).
RESULTS: At baseline, the frequencies of Th1, Th17 and Th22 cells were higher in psoriasis patients compared to the healthy controls. The expression of transcription factors T-bet, RORγt and AHR, and the serum levels of IFN-γ, IL-17, IL-22, IL-6 and TNF-α were higher in psoriasis patients compared to the healthy controls. After adalimumab therapy, there was a significant decline in the frequencies of Th1, Th17 and Th22 cells, and a concomitant decrease in the levels of their associated transcription factors and cytokines.
CONCLUSIONS: The results suggest that the anti-tumor-necrosis-factor antagonist, adalimumab, disrupts the Th1, Th17 and Th22 pathways, resulting in clinical improvement of psoriasis.