99Tc-methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδT cells and CD4+CD25+Foxp3+Tregs
99Tc-methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδT cells and CD4+CD25+Foxp3+Tregs
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DOI：
10.1111/1756-185x.12292
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发表时间：
2016-06-01
影响因子：
2.5
通讯作者：
Sun, Lingyun
中科院分区：
文献类型：
--
作者：
Su, Dinglei;Shen, Minning;Sun, Lingyun
目的T细胞在类风湿关节炎（RA）的发病机制中发挥重要作用。近年来，许多研究利用氨基二膦酸盐的T细胞活化能力来治疗恶性肿瘤。以Tc-99-亚甲基二膦酸盐计Tc-99-MDP长期以来在中国广泛用于治疗RA，疗效良好，目的探讨Tc-99-MDP对RA患者外周血T细胞及CD 4（+）、CD 25（+）、Foxp 3（+）的影响。方法对19例活动期RA患者静脉注射99-Tc-MDP 20 g/d，连续10- 14 d。在治疗前和治疗后，对每个患者的主要临床和实验室参数进行评估。流式细胞仪检测CD 3（++）T细胞和CD 4（+）CD 25（+）Foxp 3（+）T细胞的比例。结果Tc 99-MDP治疗后，外周血CD 3（++）T细胞和CD 4（+）CD 25（+）Foxp 3（+）T细胞比例明显升高，CD 4（+）CD 25（+）Foxp 3（+）T细胞比例明显升高，CD 4（+）CD 25（+）Foxp 3（+）Foxp 3（+）T细胞比例明显升高。血清TNF-α、IL-6水平降低，血清TGF-β水平升高。结论（99）Tc-MDP可能通过上调RA患者外周血T细胞和CD 4（+）CD 25（+）Foxp 3（+）T淋巴细胞的比例，以及通过上调TGF-β、降低TNF-β和IL-6影响血清细胞因子环境，从而改善RA的活动性。
Aim T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As Tc-99-methylene diphosphonate (Tc-99-MDP) has long been widely used for the treatment of RA in China with good efficacy, we are interested in whether this drug exerts its therapeutic effect on RA by modulating peripheral T cells of RA patients.ObjectivesTo investigate the effect of Tc-99-MDP on the frequency of T cells and CD4(+)CD25(+)Foxp3(+)Tregs in the peripheral blood of patients with active RA.MethodsNineteen patients with active RA were treated with Tc-99-MDP intravenously at a dose of 20g/day consecutively for 10-14days. Before and after treatment, the main clinical and laboratory parameters for each patient were evaluated. The frequency of CD3(++)T cells and CD4(+)CD25(+)Foxp3(+)Tregs was detected by flow cytometry. Serum levels of interferon (IFN)-, tumor necrosis factor (TNF)-, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)- were measured with enzyme-linked immunosorbent assay.ResultsAfter intravenous Tc-99-MDP therapy, the frequency of peripheral CD3(++)T cells and CD4(+)CD25(+)Foxp3(+)Tregs were significantly elevated, paralleled with decreased serum levels of TNF- and IL-6 and increased level of serum TGF-. The elevation of peripheral CD3(++)T cells was positively correlated with increased serum TGF- and decreased disease activity.Conclusion(99)Tc-MDP may improve the activity of RA through upregulating the frequency of peripheral T cells and CD4(+)CD25(+)Foxp3(+)Tregs as well as affecting the serum cytokine environment by increasing TGF- and decreasing TNF- and IL-6.