甲巯咪唑治疗Graves 病诱发白细胞减少患者 Th17/Treg 细胞及相关因子的变化及意义

Changes and significances of Th17/Treg cells in patients with leukopenia induced by methimazole in the treatment of graves disease

摘要:

目的 探讨Th17、Treg 细胞及相关因子在甲巯咪唑治疗Graves 病诱发白细胞减少患者治疗前 外周血中的变化及意义。方法 选取2017 年12 月—2018 年6 月于沧州市人民医院收治的初发Graves 病患 者作为研究对象，给予甲巯咪唑治疗3 个月，依据白细胞减少的标准分为白细胞减少组和正常白细胞组，另选 取同期该院的健康体检群众作为对照组。采集受试者空腹外周静脉血，采用流式细胞仪测定Th17、Treg 细 胞的表达，采用ELISA 法检测IL-17、TGF-β 的分泌水平。结果 正常白细胞组、白细胞减少组FT3、FT4、 TgAb、TPO-Ab 及TRAb 较对照组高（P <0.05），TSH 较对照组低（P <0.05）。正常白细胞组、白细胞减少 组Th17 细胞在CD4+T 细胞中的百分比均较对照组高（P <0.05）。白细胞减少组、正常白细胞组Treg 细胞 在CD4+T 细胞中的百分比较对照组低（P <0.05）。正常白细胞组、白细胞减少组Th17/Treg 均较对照组高 （P <0.05）。白细胞减少组、正常白细胞组IL-17、IL-17/TGF-β 较对照组高（P <0.05），TGF-β 较对照组 低（P <0.05）。结论 甲巯咪唑治疗Graves 病诱发白细胞减少患者在治疗前外周血Th17、Treg 细胞及相关 细胞因子异常表达，并向Th17 细胞漂移，提示Th17/Treg 细胞免疫失衡在甲巯咪唑诱发白细胞减少发病机制 中发挥重要作用。

Abstract:

Objective To investigate the changes and significance of Th17 cells, Treg cells and related cytokines in the peripheral blood of patients with leukopenia induced by methimazole in the treatment of Graves disease. Methods Patients with primary GD who were admitted to our hospital from December 2017 to June 2018 were enrolled in the study. They were treated with methimazole for 3 months. According to the criteria for leukopenia, 30 patients were divided into leukopenia group (LP group), 35 patients in the Non-leukopenia group (NLP group) and 50 healthy subjects were selected as the control group. The fasting peripheral venous blood of the subjects was collected. The expression of Th17 cells and Treg cells was detected by flow cytometry. The expressions of interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) were detected by ELISA. Results The levels of FT3, FT4, TgAb, TPO-Ab and TRAb in the LP group and the NLP group were higher than those in the control group (P < 0.05), and the level of TSH was lower (P < 0.05); The percentages of Th17 cells in CD4+ T cells in NLP group and LP group were higher than those in control group (P < 0.05). Th17/Treg ratios in NLP group and LP group was higher than that in control group (P < 0.05). IL-17 and IL-17/TGF-β ratios in LP group and NLP group were higher than those in control group (P < 0.05), and TGF-β was lower than that in control group (P < 0.05). Conclusions The expressions of peripheral blood Th17, Treg and related cytokines in patients with leukopenia induced by methimazole in the treatment of Graves disease are abnormally expressed, and drifts to Th17 cells, sugessting that Th17/Treg imbalance plays a vital role in the pathogenesis of leukopenia induced by methimazole.