摘要目的 探讨SLE患者外周血Th17及CD4+ CDhigh25Treg细胞及相关细胞因子IL-17、IL-21、TGF-β和IL-10的水平变化及意义.方法 选取2009-2010年河南省人民医院56例SLE患者(非活动期26例、活动期30例)及28名健康对照者.采用流式细胞术检测外周血单个核细胞中Th17及CD4+ CDhigh25 Treg细胞水平；采用QRT-PCR检测RORγt mRNA和Foxp3 mRNA的表达水平；采用ELISA检测血浆IL-17、IL-21、TGF-β和IL-10水平,并分析其与SLE的相关性.结果 SLE患者组外周血Th17细胞水平为(3.44±0.96)％,显著高于健康对照组的(2.42±0.52)％,差异有统计学意义(t=5.38,P=0.000).SLE患者组外周血CD4+CDhigh25Treg细胞水平为(1.32±0.57)％,显著低于健康对照组的(2.07±0.67)％,差异有统计学意义(t=3.28,P=0.034).SLE患者的RORγt mRNA表达水平为(0.219±0.063),高于健康对照组的(0.087±0.045),差异有统计学意义(t=6.41,P=0.000)；而SLE患者的Foxp3+ mRNA表达水平为(0.063±0.045),低于健康对照组的(0.128±0.056),差异有统计学意义(t=5.28,P=0.000).SLE患者组IL-17、IL-21、IL-10水平分别为122.4(60.5～188.3)、167.2(128.7 ～871.4)、51.3(20.9 ～123.7)ng/L,高于健康对照组的27.1(18.1 ～86.2)、31.0(31.0～424.5)、33.5(16.4～54.1) ng/L,差异有统计学意义(Z值分别为3.83、4.54、1.87,P均＜0.05),TGF-β水平为31.0(31.0 ～168.6) ng/L,低于健康对照组的159.8(63.4～389.7)ng/L,差异有统计学意义(Z=4.87,P＜0.05).SLE患者血浆IL-17水平与Th17细胞水平、SLEDAI积分、抗dsDNA抗体水平呈显著正相关(r=0.621、0.581、0.512,P＜0.05),与补体C3水平呈负相关(r=-0.543,P＜0.05).CD4+ CDhigh25Treg细胞与SLEDAI积分呈负相关(r=- 0.423,P＜0.05),与补体C3水平呈正相关(r=0.511,P＜0.05).结论 SLE患者Th17细胞数量增高,CD4+ CDhigh25 Treg细胞数量减少,以及相关细胞因子的紊乱在SLE的发病机制中可能起到重要作用.

abstractsObjective To analyze the levels of Th17,CD4+ CDhigh25and the related cytokines (IL-17,IL-21,TGF-β,IL-10)in the plasma of patients with SLE.Methods The percentage of Th17 and CD4+ CDhigh25 Treg cells in peripheral blood were examined by flow cytometry.QRTPCR was used to detect the mRNA expression level of RORγt and Foxp3 of 56 SLE patients (26 patients are inactive and 30 patients are active) and 28 healthy controls.Plasma cytokines levels were measured by ELISA.Results The percentage of Th17 cells in patients with SLE was higher than that of healthy controls [ (3.44 ± 0.96) ％ vs (2.42 ± 0.52) ％,t =5.38,P =0.000 ].The percentage of CD4+ CDhigh25 Treg cells in patients with SLE was lower than that of healthy controls [ ( 1.32 ± 0.57 ) ％ vs ( 2.07 ± 0.67 ) ％,t =3.28,P =0.034].The expressions of RORγt mRNA was increased compared with healthy controls[ (0.219 ±0.063) vs (0.087 ± 0.045 ),t =6.41,P =0.000 ],but the expressions of Foxp3 mRNA was decreased compared with healthy controls [ (0.063 ±0.045) vs (0.128 ±0.056),t =5.28,P =0.000].Plasma levelsof IL-17,IL-21 and IL-10 in SLE patients were 122.4 ( 60.5 - 188.3 ),167.2 ( 128.7 - 871.4 ),51.3(20.9 - 123.7 ) ng/L,respectively,and in the control group were 27.1 ( 18.1 - 86.2 ),31.0 ( 31.0 -424.5),33.5( 16.4 - 54.1 ) ng/L,respectively,they were significantly different between the two groups (Z =3.83,4.54,1.87,all P ＜ 0.05 ).However,TGF-β levels were markedly decreased in SLE patients compared with controls [ 31.0 ( 31.0 - 168.6 ) ng/L vs 159.8 ( 63.4 - 389.7 ) ng/L,Z =4.87,P ＜0.05.IL-17 was positive correlation with Th17 cells,SLEDAI score,dsDNA antibody titers ( r =0.621,0.581,0.512,respectively,all P ＜ 0.05 ),but was negative correlation with C3 ( r =- 0.543,P ＜ 0.05 ) in SLE patients.Although the percentage of CD4 + CDhigh25 Treg cells were negatively correlated with SLEDAI score ( r =- 0.423,P ＜ 0.05 ),it was positively correlated with C3 ( r =0.511,P ＜ 0.05 ).Conclusion This study suggests that the imbalance of Th17 cells and CD4+ CDhigh25 Treg cells and the disorder of related cytokines are important in the pathogenesis of SLE patients.