慢性原发性血小板减少症患者外周血辅助性T细胞17和调节性T细胞比例变化及其意义

Changes and significance of helper T cells 17 and regulatory T cells in patients with chronic primary thrombocytopenia

目的通过测定慢性原发性血小板减少症（cITP）患者治疗前、后的外周静脉血辅助性T细胞（Th）17和调节性T细胞（Treg）比例变化，探讨其在clTP发病和治疗中的作用及临床意义。方法选取2012年1月至2015年12月于山东省菏泽市中医医院就诊的经。肾上腺糖皮质激素治疗无效的31例clTP患者为研究对象，按照治疗结果将其分为有效组（n=22）和无效组（n=9）。选择同期于同一家医院进行体检的2l例健康个体纳入对照组（n=21）。采用流式细胞术测定cITP患者治疗前、后和对照组健康个体的外周静脉血Th17和Treg比例变化，计算Thl7／Treg。Thl7、Treg比例和Thl7／Treg等呈非正态分布计量资料采用M（P25～P75）表示，其组间比较及组内治疗前、后比较采用Mann-WhitneyU检验。本研究征得受试者的知情同意，并与之签署临床研究知情同意书。3组受试者的年龄、性别构成比等一般临床资料比较，差异均无统计学意义（P〉0．05）。结果①治疗前，有效组和无效组Th17、Treg比例及Th17／Treg分别比较，差异均无统计学意义（Z=0．231、0．243、0．305，P=0．993、0．984、0．814）；治疗前，有效组、无效组分别与对照组上述3项指标进行比较，差异均有统计学意义（Z=4．023、5．317、6．231、4．892、4．912、6．042，P=0．002、0．002、0．001、0．001、0．003、0．001）。②有效组治疗前Thl7、Treg比例及Thl7／Treg与治疗后分别比较，差异均有统计学意义（Z=3．591、3．225、5．254，P=0．003、0．006、0．001）；治疗后，有效组与对照组上述3项指标分别比较，差异均无统计学意义（Z=0．342、0．391、0．328，P=0．871、0．882、0．789）。③无效组治疗前Th17、Treg比例及Th17／Treg与治疗后分别比较，差异均无统计学意义（Z=0．207、0．194、0．284，P=0．991、0．996、0．901）；治疗后，无效组与对照组上述3项指标分别比较，差异均有统计学意义（Z=4．358、4．465、5．612，p=0．002、0．003、0．001）。结论Thl7、Treg可能参与cITP的发生、发展。cITP患者存在Treg及Thl7比例异常和Treg／Th17平衡失调。针对Treg／Th17异常的靶向药物有望为治疗cITP开辟新的途径。

Objective To study the changes of helper T cells （Th） 17 and regulatory T cells （Treg） before and after therapy in patients with chronic primary thrombocytopenia（cITP）, in order to explore their significance in pathogenesis and treatment of cITP. Methods From January 2012 to December 2015, a total of 31 patients with cITP who were treated in Heze Hospital of Traditional Chinese Medicine were included in this study. They were divided into effective group （n=22） and ineffective group （n= 9） according to their treatment effects. Meanwhile, there were 21 healthy individuals for physical examination were also included in this study as control group （n=21）. The proportion of plasma ThlT, Treg and the ratio of Thl7/Tregs before and after therapy in patients with cITP and healthy adults in control group were detected by flow cytometry. The data of Th17, Tregs and the ratio of Th17/Tregs were non-normal distributions, and measurement data were expressed as M（P25-P75 ）. Mann-Whitney U test was used to compare the data among deffierent groups and between before and after therapy in the same group. The research subjects were told and signed the informed consent agreement. There were no significant differences among three groups in the age and aspects of gender ratio, etc. （P〉0. 05）. Results ① Before therapy, proportion of plasma Th17, Tregs and the ratio of Thl7/Tregs were no significance difference between effective group and ineffective group（Z=0. 231, 0. 243, 0. 305; P=0. 984, 0. 993, 0. 814）, but compared with control group espectively, both effective group and ineffective group had statistically differences （Z= 4. 023, 5. 317, 6. 231, 4. 892, 4. 912, 6. 042; P=0.002, 0.002, 0.001, 0.001, 0.003, 0.001）. ② In effective group, there were significance differences in proportion of plasma Th17, Tregs and the ratio of ThlT/Tregs between before and after therapy （Z=3. 591, 3. 225, 5. 254; P=0. 003, 0. 006, 0. 001） ;but after therapy, the difference was no statistically significant between effective group and control group （Z=0. 342, 0. 391, 0. 328; P= 0. 871, 0. 882, 0. 789）. ③ In ineffective group, there were no significance difference in proportion of plasma Thl7, Tregs and the ratio of Th17/Tregs between before and after therapy （Z=0.207, 0. 194, 0. 284;P= 0. 991, 0. 996, 0. 901）. And after therapy, the differences still had statistically significance between ineffective group and control group （Z=4. 358, 4. 465, 5. 612; P= 0. 002, 0. 003, 0. 001）. Conclusions Thl7 and Treg may participate in the occurrence and development of cITP. Patients with clTP have abnormal proportion of plasma Treg and Th17 and dysregulation of Treg/Th17. Targeted drugs targeting Treg/Th17 abnormalities are also expected to open up new avenues for the treatment of cITP.