Early and late effect of infliximab on circulating dendritic cells phenotype in rheumatoid arthritis patients.

A Balanescu, E Radu, R Nat, T Regalia, V Bojinca, R Ionescu, S Balanescu, C Savu, D Predeteanu
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Abstract

The aim of this study was to analyze the phenotype of circulating dendritic cells (DCc) in rheumatoid arthritis (RA) patients before and after treatment with infliximab (at 24 h and 6 months) and the correlation between these changes and the clinical response to treatment. Sixteen patients with RA were recruited and clinical status was determined using the Disease Activity Score 28 (DAS28). All patients had active disease (mean DAS28 = 5.96) and were suitable for treatment with infliximab. Samples of peripheral venous blood were obtained before administration of the first dose of infliximab and again at 24 h and 6 months after treatment. DCc populations were analyzed by flow cytometry. At 24 h, there were no differences in the clinical status of the patients. However, we found a decrease in CD11c+ and, to a lesser extent, CD123+ DCc percentages. The expression of CD83, the most important activation marker for DC, was also shown to be decreased 24 h after infliximab therapy. After 6 months of treatment, all patients showed significant clinical improvement (mean DAS28 = 3.64, p < 0.001) and expression of the activation marker on DCc remained low. In conclusion, this study supports the role of tumor necrosis factor (TNF)-alpha blockade in preventing the maturation of DCc and in reducing the expression of their activation markers. Although the clinical response to infliximab was not observed after 24 h, DCc activation was strongly reduced by anti-TNF-alpha therapy. After 6 months of treatment, current data show a less active phenotype of DCc associated with clinical improvement in all patients in the study.

英夫利西单抗对类风湿关节炎患者循环树突状细胞表型的早期和晚期影响
本研究旨在分析类风湿性关节炎(RA)患者在接受英夫利西单抗治疗前后(24 小时和 6 个月)循环树突状细胞(DCc)的表型,以及这些变化与临床治疗反应之间的相关性。研究人员招募了16名类风湿关节炎患者,并使用疾病活动度评分28(DAS28)确定其临床状态。所有患者的疾病均处于活动期(平均 DAS28 = 5.96),适合接受英夫利西单抗治疗。在服用第一剂英夫利西单抗前采集外周静脉血样本,并在治疗后24小时和6个月再次采集样本。流式细胞术分析了DCc群。24小时后,患者的临床状态没有差异。但是,我们发现 CD11c+ DCc 的百分比有所下降,CD123+ DCc 的百分比也有所下降。英夫利西单抗治疗 24 小时后,CD83(DC 最重要的活化标志物)的表达也有所下降。治疗 6 个月后,所有患者的临床症状均有明显改善(平均 DAS28 = 3.64,p < 0.001),而 DCc 上的活化标记物表达仍然较低。总之,本研究支持肿瘤坏死因子(TNF)-α阻断剂在阻止DCc成熟和降低其活化标志物表达方面的作用。虽然英夫利昔单抗治疗 24 小时后未观察到临床反应,但抗肿瘤坏死因子-α疗法却大大降低了 DCc 的活化。经过 6 个月的治疗后,目前的数据显示 DCc 表型的活性降低,与此同时,研究中所有患者的临床症状都得到了改善。
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