IgA肾病外周血单个核细胞T-bet GATA-3 ROR-γt和Foxp3 mRNA的表达及其意义研究

T-bet,GATA-3,ROR-γt and Foxp3 mRNA levels of helper T cells in peripheral blood mononuclear cells from patients with IgA nephropathy

目的在mRNA水平探讨IgA肾病患者外周血Th1、Th2、Th17和Treg细胞免疫失衡及其与IgA肾病(IgAN)牛津分型的相关性。方法以2010年11月至2011年11月在大连医科大学附属第一医院肾内科经肾活检病理确诊的原发性IgAN患者为研究对象,应用实时荧光定量PCR检测IgAN患者(20例)和健康对照组(10名)外周血单个核细胞的特异性转录因子T-bet、GATA-3、ROR-γt、Foxp3的mRNA表达水平。结果与对照组比较,IgAN组ROR-γt表达明显升高(P<0.05)、Foxp3表达明显下降(P<0.05),且ROR-γt/Foxp3比值明显升高(P<0.05);而T-bet、GATA-3的表达与对照组相比差异无统计学意义(P>0.05)。按IgAN牛津分型病理指标分组结果比较显示,M1组T-bet表达及T-bet/GATA-3的比值较M0组明显升高(P<0.05)。进一步相关分析显示,IgAN组T-bet表达与系膜增殖积分呈显著正相关(r=0.541,P<0.01)。S1组T-bet表达显著升高(P<0.01),ROR-γt表达无明显差异(P>0.05),T-bet/ROR-γt比值明显升高(P<0.05);而GATA-3、Foxp3无变化(P>0.05)。结论 IgAN患者外周血单个核细胞在mRNA水平出现了偏向Th17极化,而Treg的应答被抑制。IgAN系膜增殖程度与Th1极化呈正相关,而肾小球节段硬化的Th1/Th17的比值明显升高。

Objective To investigate the T-bet, GATA-3, ROR-γt and Foxp3 mRNA expression levels in peripheral blood mononuclear cells （PBMCs） from patients with IgA nephropathy and their correlations with Oxford Classification of IgA ne- phropathy. Methods Twenty patients with IgA nephropathy diagnosed in our hospital from November 2010 to 2011 and ten healthy volunteers were included in this study. Real time quantitative polymerase chain reaction （RT-PCR） was used to de- tect the T-bet, GATA-3, ROR-γt and Foxp3 mRNA expression levels in PBMCs from the two groups. Results ROR-γt mR- NA expression levels and the ratio of RORγt/Foxp3 in patients with IgA nephropathy were higher while Foxp3 mRNA lev- els were lower than those in the controls （ both P 〈 0. 05 ）. According by Oxford Classification of IgA nephropathy, T-bet mRNA expression levels and the ratio of T-bet/GATA-3 in the M1 group were high than those in the M0 group （ P 〈 0. 05 ） , and correlation analysis showed that T-bet mRNA expression was associated with mesangial hypercellularity score （r = 0. 541 ,P 〈0. 01 ）. T-bet mRNA expression levels and the ratio of T-bet/ROR-γt in the S1 group were higher than those in the SO group （ P 〈 0. 05 ）. No significantly differences were detected in GATA-3 and Foxp3 mRNA expression levels be- tween in the SO and S1 groups （P 〉 0. 05）. Conclusion There are polarization of Thl and Thl7 in patients with IgA ne- phropathy. The Treg response is inhibited. Thl polarization is positively correlated with mesangial hypercellularity score. The ratio of Thl/Thl7 is elevated in IgA nephropathy patients in whom segmental glomerulosclerosis exists.