系统性硬皮病患者外周血Th17／Treg细胞与病情活动的相关性

Relationships of peripheral blood Thl7 and regulatory T cells with disease activity in patients with systemic sclerosis

目的 探讨系统性硬皮病（SSc）患者外周血Th 17/Treg细胞与病情活动的相关性.方法 45例SSc患者中活动组21例,非活动组24例,正常人对照组24例.用流式细胞仪检测外周血Th17、Treg细胞各占CD4＋细胞的百分比.荧光定量PCR法检测外周血单一核细胞（PMBC）中白介素17A（IL-17A）、维A酸类核孤儿受体γ（RoRγt）、叉头状螺旋转录因子3（FoxP3）mRNA水平.酶联免疫吸附试验检测血清IL-17水平.结果 ①SSc活动组、非活动组和正常人对照组外周血Th17细胞占CD4＋细胞的百分比分别为2.34±1.19、0.68±0.39和0.57±0.49,活动组显著高于非活动组、正常人对照组（P＜0.05）.3组外周血Treg细胞比例差异无统计学意义（P＞0.05）；②SSc活动组、非活动组和正常人对照组外周血IL-17水平分别为53.60±9.90、15.18±3.24、15.53±4.12 pg/ml,对照组和非活动组均显著低于活动组（P＜0.05）；③SSc活动组、非活动组和对照组3组外周血细胞IL-17A mRNA表达水平分别为11.73±0.80、9.77±1.30、10.79±0.74,活动组显著高于对照组、非活动组（P＜0.05）；3组外周血细胞中RoRγt mRNA表达水平分别为18.48±1.09、15.89±1.48、17.77±1.64,活动组显著高于对照组和非活动组（P＜0.05）,3组外周血细胞FoxP3mRNA表达水平差异无统计学意义（P＞0.05）；④外周血Th17细胞比例、血清IL-17水平与活动组SSc患者的病情活动度呈正相关,分别为r=0.675（P＜ 0.05）、r=0.644（P＜ 0.05）.结论 Th17细胞亚群在活动期SSc患者体内扩增,其扩增与SSc活动密切相关.

Objective To evaluate the relationship of peripheral blood Th17 and regulatory T （Treg） cells with disease activity in patients with systemic sclerosis （SSc）.Methods This study recruited 21 patients with active SSc,24 patients with inactive SSc and 24 normal human controls with informed consent.Peripheral blood samples were obtained from these subjects.Flow cytometry was used to detect the percentages of Th17 and Treg cells in peripheral blood CD4＋ cells,a fluorescence-based quantitative PCR to determine the levels of interleukin （IL）-17A,retinoid-related orphan receptor gamma t （RoRγt）,forkhead box P3 （FoxP3） mRNA in peripheral blood mononuclear cells （PMBCs）,and enzyme linked immunosorbent assay to measure the serum level of IL-17.Results Increased percentage of Th17 cells in peripheral blood CD4＋ cells was observed in patients with active SSc compared with those with inactive SSc and normal human controls （2.34% ± 1.19%vs.0.68% ± 0.39% and 0.57% ± 0.49%,respectively,both P 〈 0.05）.No statistical difference was noted in the percentage of Treg cells in CD4＋ cells or the mRNA expression levels of FoxP3 between the patients with active SSc,inactive SSc and normal human controls （all P 〉 0.05）.There was a significant increase in the mRNA expression of IL-17A,RoRγt in PBMCs and serum levels of IL-17 in patients with active SSc compared with patients with inactive SSc and normal human controls （ 11.73 ± 0.80 vs.9.77 ± 1.30 and 10.79 ± 0.74,respectively,both P 〈 0.05; 18.48 ± 1.09 vs.15.89 ± 1.48 and 17.77 ± 1.64,respectively,both P 〈 0.05; 53.60± 9.90 pg/ml vs.15.18 ± 3.24 pg/ml and 15.53 ± 4.12 pg/ml,respectively,both P 〈 0.05）.The percentage of Th17 cells in CD4＋ cells and serum IL-17 levels were both positively correlated with disease activity in patients with active SSc （r =0.675,0.644,respectively,both P 〈 0.05）.Conclusions Th17 cells are highly proliferative in patients with active SSc,which may be closely correlated with the activity of SSc.