幼年特发性关节炎患儿外周血CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞比例降低且与细胞因子水平负相关

The decreased proportion of CD4^(+)CD25^(+)FOXP3^(+)regulatory T cells in peripheral blood of children with juvenile idiopathic arthritis and its negative correlation with cytokine level

目的探讨幼年特发性关节炎(JIA)患儿外周血CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞与白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)的水平及临床意义。方法采用流式细胞术检测58例JIA患儿及40例体检健康儿童外周血中CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞比例,收集每例患儿对应的血清,化学发光法检测JIA患儿血清中IL-6、TNF-α水平。Pearson相关性分析JIA患儿外周血CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞比例与血清IL-6、TNF-α水平的关系。在58例JIA患儿中收集到18例JIA全身型患儿对应的托珠单抗(tocilizumab)治疗后的全血及血清样本,采用以上方法检测托珠单抗治疗前后外周血CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞与血清IL-6、TNF-α水平。结果与健康对照组相比,JIA患儿CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞比例明显降低,血清IL-6、TNF-α水平明显增高;多关节型与全身型JIA患儿CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞、IL-6及TNF-α的水平无明显变化;JIA患儿外周血CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞比例与血清IL-6、TNF-α水平呈负相关关系(r=-0.468,r=-0.415),JIA患儿血清IL-6与TNF-α水平呈现正相关关系(r=0.613)。与托珠单抗治疗前相比,JIA患儿托珠单抗治疗后CD4^(+)CD25^(+)FOXP3^(+)调节性T细胞比例显著升高但仍明显低于健康对照组;治疗后IL-6水平显著降低但仍显著高于健康对照组;治疗后TNF-α水平略下降但差异不明显。结论幼年特发性关节炎患儿调节性T细胞比例降低,与IL-6、TNF-α水平负相关,托珠单抗治疗后CD4^(+)CD25^(+)FOXP3^(+)调节T性细胞比例增加、IL-6水平减低,可用于监测JIA全身型的病情活动与药物疗效。

Objective To investigate the expression of CD4^(+)CD25^(+)FOXP3^(+)regulatory T cells(Tregs),IL-6 and TNF-αin patients with juvenile idiopathic arthritis(JIA)and its clinical significance.Methods The percentages of CD4^(+)CD25^(+)FOXP3^(+)Tregs in 58 children with JIA and 40 healthy controls were detected by flow cytometry.Serum levels of IL-6 and TNF-αin each patient was detected by chemiluminescence.The correlations between the expression of CD4^(+)CD25^(+)FOXP3^(+)Tregs and IL-6,TNF-αwere analyzed by pearson correlation analysis.We measured the expression level of CD4^(+)CD25^(+)FOXP3^(+)regulatory T cells,IL-6 and TNF-αof 18 cases six weeks after the treatment of tocilizumab(TCZ)in order to figure out the dynamic changes using methods above.Results The percentages of CD4^(+)CD25^(+)FOXP3^(+)Tregs in juvenile idiopathic arthritis were significantly lower than those in 40 healthy volunteers,while levels of IL-6 and TNF-αwere significantly higher.However,no obvious difference in the levels of CD4^(+)CD25^(+)FOXP3^(+)Tregs,IL-6 or TNF-αwas observed between patients with systemic and poly-articular JIA.Pearson correlation analysis showed that the percentages of CD4^(+)CD25^(+)FOXP3^(+)Tregs negatively correlated with the levels of IL-6 and TNF-α,while levels of IL-6 positively correlated with the levels of TNF-α.Compared with pre-treatment of TCZ,levels of CD4^(+)CD25^(+)FOXP3^(+)Tregs in post-treatment markedly increased,which however were still lower than control group while the levels of IL-6 significantly decreased,yet remained higher than control group.There was no statistical difference between post and pre-treatment in the levels of TNF-α.Conclusion The percentages of CD4^(+)CD25^(+)FOXP3^(+)Tregs in peripheral blood of JIA children decreases,and it has a negative correlation with IL-6 and TNF-α.Furthermore,the levels of CD4^(+)CD25^(+)FOXP3^(+)Tregs and IL-6 are partially restored after treatment with TCZ,which may be helpful to assess the activity of systemic JIA and the efficacy of therapy.