Wang Gang, Lai Fernand M-M, Tam Lai-Shan, Li Edmund K-M, Kwan Bonnie C-H, Chow Kai-Ming, Li Philip K-T, Szeto Cheuk-Chun
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Rheumatology (Oxford). 2009 Jul;48(7):755-60. doi: 10.1093/rheumatology/kep074. Epub 2009 May 20.
Regulatory T lymphocytes (Tregs) probably play an important role in the pathogenesis of SLE.
We quantified messenger RNA (mRNA) expression of FOXP3, a critical regulator for the development and function of Tregs, in the urinary sediment of 25 subjects with active lupus nephritis (LN), 17 with inactive lupus and 7 healthy subjects.
We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (24.5 +/- 45.8 vs 0.8 +/- 1.0 vs 0.6 +/- 0.8 copy; P < 0.001). In the active group, urinary FOXP3 mRNA expression level was higher in patients with proliferative LN than non-proliferative nephritis (34.6 +/- 56.3 vs 2.7 +/- 2.1 copy; P = 0.019). Urinary FOXP3 mRNA level significantly correlated with SLEDAI (r = 0.668; P < 0.001) and proteinuria (r = 0.414; P = 0.006). In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (r = 0.541; P = 0.009) and marginally with intra-renal FOXP3 mRNA level (r = 0.360; P = 0.08). Urinary FOXP3 mRNA in patients with no response to therapy was higher than those with partial response or complete response (57.6 +/- 69.8 vs 2.4 +/- 1.9 copies; P = 0.02).
We concluded that urinary FOXP3 mRNA is markedly up-regulated in patients with active LN, and the level of expression is closely correlated with the clinical and histological disease activity. A high urinary FOXP3 mRNA in LN predicts a poor therapeutic response. Measurement of FOXP3 mRNA in urine sediment may be a non-invasive biomarker for assessing the severity and risk stratification in LN.
调节性T淋巴细胞（Tregs）可能在系统性红斑狼疮（SLE）的发病机制中起重要作用。
我们对25例活动性狼疮性肾炎（LN）患者、17例非活动性狼疮患者和7例健康受试者尿沉渣中Tregs发育和功能的关键调节因子FOXP3的信使核糖核酸（mRNA）表达进行了定量分析。
我们发现，活动性LN患者尿液中FOXP3的表达水平显著高于非活动性狼疮患者和健康对照（24.5±45.8 vs 0.8±1.0 vs 0.6±0.8拷贝；P<0.001）。在活动组中，增殖性LN患者尿液中FOXP3 mRNA表达水平高于非增殖性肾炎患者（34.6±56.3 vs 2.7±2.1拷贝；P=0.019）。尿液中FOXP3 mRNA水平与SLE疾病活动指数（SLEDAI）显著相关（r=0.668；P<0.001），与蛋白尿也显著相关（r=0.414；P=0.006）。在活动组中，尿液中FOXP3 mRNA水平还与组织学活动指数显著相关（r=0.541；P=0.009），与肾内FOXP3 mRNA水平呈边缘相关（r=0.360；P=0.08）。治疗无反应患者尿液中FOXP3 mRNA高于部分反应或完全反应患者（57.6±69.8 vs 2.4±1.9拷贝；P=0.02）。
我们得出结论，活动性LN患者尿液中FOXP3 mRNA明显上调，其表达水平与临床和组织学疾病活动密切相关。LN患者尿液中高FOXP3 mRNA预示治疗反应不佳。检测尿沉渣中FOXP3 mRNA可能是评估LN严重程度和风险分层的一种非侵入性生物标志物。
