成人原发性肾病综合征中Th17/Treg免疫平衡及泼尼松对其影响的研究

Effect of prednisone on Th17/Treg immune balance in adult patients with primary nephritic syndrome

目的研究成人原发性肾病综合征(primary nephrotic syndrome,PNS)患者外周血辅助性T细胞17(Th17)和调节性T细胞(Treg)的变化,探讨Th17/Treg免疫平衡在成人PNS发病中的作用以及泼尼松治疗成人PNS过程中对Th17/Treg免疫平衡的影响。方法选取初次就诊,经泼尼松治疗有效的患者65例,以年龄、性别匹配的25名健康体检者做为正常对照组,使用流式细胞术检测正常对照组和泼尼松治疗前、后患者外周血Th17细胞和Treg细胞比例,使用酶联免疫吸附试验(ELISA)法检测血清白细胞介素(interleukin,IL)-17和IL-10的水平,使用全自动生化分析仪检测24 h尿蛋白定量,分析Th17与其相关因子IL-17的相关性以及Treg与其相关因子IL-10的相关性,分析Th17/Treg比值与24 h尿蛋白定量的相关性。结果 PNS患者外周血Th17细胞比例为(2.44%±0.58%),较正常对照组的(0.93%±0.41%)明显升高,而PNS患者Treg细胞比例为(2.28%±0.63%),较正常对照组的(3.83%±1.06%)明显降低。经泼尼松治疗后,患者外周血Thl7细胞比例为(1.02%±0.51%),较治疗前明显降低,而Treg细胞比例为(3.69%±0.82%),较治疗前明显升高,差异均具有统计学意义(P<0.05)。外周血Th17、Treg与相关细胞因子IL-17、IL-10的变化与两类细胞的变化一致。Th17/Treg细胞比值与24 h尿蛋白定量呈显著正相关(r=0.826,P<0.01)。结论 Th17/Treg免疫失衡与成人PNS发生密切相关,泼尼松可能通过调节Th17/Treg免疫平衡影响成人PNS的发展,检测外周血Th17/Treg细胞比值的变化可做为成人PNS的辅助诊断指标以及泼尼松治疗成人PNS疗效评价指标。

Objective To investigate whether the Th17/Treg immune balance was broken in adult patients with primary nephritic syndrome and to explore the possible role of Th17/Treg immune balance in the pathogenesis of primary nephritic syndrome and how prednisone inflences the Th17/ Treg immune balance during treatiment of adult PNS. Methods Twenty-five healthy volunteers served as healthy controls and 65 prednisone-effective adult patients with PNS were enrolled in this study. Blood samples were obtained from healthy control group and patients with PNS before and after treat- ment. The frequencies of peripheral Th17 and Treg were evaluated by flow cytometry. The concentra- tions of plasma IL-17 and IL-10 were tested by ELISA. Proteinuria levels were detected by automatic biochemical analyzer. Correlations between peripheral Th17, Treg frequencies and concentrations of related cytokines IL-17, IL-10 were analyzed. Correlation between Th17/Treg ratios and proteinuria levels was analyzed. Results As compared with healthy controls, the frequencies of peripheral Th17 increased significantly （2. 44% ± 0. 58% vs. 0. 93% ± 0. 41%）, and those of Treg decreased significantly （2. 28% ±0. 63% vs. 3. 83% ± 1.06%）. After prednisone treatment, PNS patients exhibited a significant decrease in the frequencies of Th17 （1.02% ± 0. 51%）, and the frequencies of Treg in- creased markedly （3. 69% ± 0. 82%）. All these results showed significant differences. Besides, IL-17 concentrations were positively correlated with frequencies of peripheral Th17, and IL-10 concentrations were positively correlated with frequencies of peripheral Treg. Th17/Treg ratios were positively correlated with proteinuria levels. Conclusions Th17/Treg imbalance may be involved in the pathogenesis of primary nephritic syndrome. Effective prednisone therapy may maintain Th17/Treg immune balance in adult PNS patients. Th17/Treg ratios may be used as an accessory diagnosis marker for adults with PNS and therapeutic effect evaluation for prednisone treatment.