Wu Tianfu, Xie Chun, Wang Hong W, Zhou Xin J, Schwartz Noa, Calixto Sergio, Mackay Meggan, Aranow Cynthia, Putterman Chaim, Mohan Chandra
Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75235, USA.
J Immunol. 2007 Nov 15;179(10):7166-75. doi: 10.4049/jimmunol.179.10.7166.
In an effort to identify potential biomarkers in lupus nephritis, urine from mice with spontaneous lupus nephritis was screened for the presence of VCAM-1, P-selectin, TNFR-1, and CXCL16, four molecules that had previously been shown to be elevated in experimental immune nephritis, particularly at the peak of disease. Interestingly, all four molecules were elevated approximately 2- to 4-fold in the urine of several strains of mice with spontaneous lupus nephritis, including the MRL/lpr, NZM2410, and B6.Sle1.lpr strains, correlating well with proteinuria. VCAM-1, P-selectin, TNFR-1, and CXCL16 were enriched in the urine compared with the serum particularly in active disease, and were shown to be expressed within the diseased kidneys. Finally, all four molecules were also elevated in the urine of patients with lupus nephritis, correlating well with urine protein levels and systemic lupus erythematosus disease activity index scores. In particular, urinary VCAM-1 and CXCL16 showed superior specificity and sensitivity in distinguishing subjects with active renal disease from the other systemic lupus erythematosus patients. These studies uncover VCAM-1, P-selectin, TNFR-1, and CXCL16 as a quartet of molecules that may have potential diagnostic significance in lupus nephritis. Longitudinal studies are warranted to establish the clinical use of these potential biomarkers.
为了确定狼疮性肾炎的潜在生物标志物，对患有自发性狼疮性肾炎的小鼠尿液进行了筛查，以检测血管细胞黏附分子-1（VCAM-1）、P-选择素、肿瘤坏死因子受体-1（TNFR-1）和CXC趋化因子配体16（CXCL16）的存在，这四种分子先前已被证明在实验性免疫性肾炎中升高，尤其是在疾病高峰期。有趣的是，在几种患有自发性狼疮性肾炎的小鼠品系（包括MRL/lpr、NZM2410和B6.Sle1.lpr品系）的尿液中，所有这四种分子的水平均升高了约2至4倍，与蛋白尿密切相关。与血清相比，VCAM-1、P-选择素、TNFR-1和CXCL16在尿液中含量丰富，尤其是在疾病活动期，并且在患病肾脏中表达。最后，狼疮性肾炎患者的尿液中这四种分子也升高，与尿蛋白水平和系统性红斑狼疮疾病活动指数评分密切相关。特别是，尿VCAM-1和CXCL16在区分活动性肾病患者与其他系统性红斑狼疮患者方面显示出更高的特异性和敏感性。这些研究揭示了VCAM-1、P-选择素、TNFR-1和CXCL16这一组分子可能在狼疮性肾炎中具有潜在的诊断意义。有必要进行纵向研究以确定这些潜在生物标志物的临床应用。
