Division of Rheumatology, UT Southwestern Medical Center at Dallas, TX 75390, USA.
Mol Cell Proteomics. 2013 May;12(5):1170-9. doi: 10.1074/mcp.M112.021667. Epub 2013 Jan 23.
There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n = 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r = 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin.
目前迫切需要鉴定系统性红斑狼疮（SLE）的生物标志物，因为 SLE 患者常伴有肾衰竭。当最近使用基于探索性阵列的蛋白质组学平台筛选狼疮肾炎患者尿液中的约 280 种分子时，发现了血管抑素水平升高。血管抑素是纤溶酶原的生物活性片段，已知其在血管生成和炎症中有调节作用。接下来，ELISA 法在另一组独立的 SLE 患者（n=100）中验证了尿血管抑素的显著升高。在 SLE 患者中，与无活动 SLE 患者相比，活动 SLE 患者的尿血管抑素显著升高，与 SLEDAI 疾病活动指数和 SLICC 肾脏活动评分相关性良好（r=0.66，p<0.0001）。ROC 曲线分析进一步证实，尿血管抑素有能力区分活动期 SLE 患者和无活动期疾病患者。IV 型狼疮肾炎患者的尿血管抑素水平最高。免疫组织化学染色将血管抑素表达定位于这些患者的肾小管细胞中。最后，当同时从 LN 患者中获得配对的尿肾样本进行检查时，尿血管抑素水平与肾脏病理慢性指数密切相关，但与活动指数无关。鉴于 IV 型狼疮肾炎和肾脏病理慢性变化预示着肾脏和患者预后不良，尿血管抑素成为 SLE 肾脏疾病的新型非侵入性标志物。正在进行纵向研究以进一步评估尿血管抑素的疾病预测潜力。
