Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis.
Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis.
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DOI：
10.1186/s13075-017-1498-3
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发表时间：
2018-01-11
影响因子：
4.9
通讯作者：
Mohan C
中科院分区：
文献类型：
--
作者：
Mok CC;Soliman S;Ho LY;Mohamed FA;Mohamed FI;Mohan C
目的：探讨尿血管抑素、CXC趋化因子配体4(CXCL4)和血管细胞黏附分子-1(VCAM-1)作为系统性红斑狼疮(SLE)肾脏疾病的生物标志物。研究对象为符合 ≥ -4美国风湿病学会诊断标准的系统性红斑狼疮患者，包括活动性肾脏疾病、活动性非肾脏疾病或非活动性疾病，以及一组健康对照。用酶联免疫吸附试验检测尿样中血管抑素、CXCL4和VCAM-1的含量，并用肌酐进行归一化。通过接收器工作特性分析获得最佳截断值，以计算与抗双链DNA(抗dsDNA)和补体C3相比，这些标记物在区分不同组患者方面的表现。这些尿液生物标志物与各种肾脏参数之间的相关性也被测试。研究对象为系统性红斑狼疮患者(n = 227例，非活动性SLE 80例，活动性非肾脏疾病67例，活动性肾病80例；女性占94%，年龄39.2 ± 13.8岁)和对照组53例(占96%)。所有人都是华裔。活动期肾病患者尿Angiostatin、CXCL4和VCAM-1水平显著高于活动期非肾病患者、稳定期SLE患者和正常对照组。这些标记物与SLE疾病总活动性指数(SLEDAI)和肾脏SLEDAI评分以及尿蛋白/肌酐比率显著相关。与血清抗dsDNA/C3抗体相比，尿Angiostatin对鉴别活动期肾脏SLE和活动期非肾性SLE的特异性和敏感性(AUC)为0.87。另一方面，尿CXCL4(AUC 0.64)和VCAM-1(AUC 0.73)的作用类似于抗dsDNA/C3。3种标志物在区分活动期和非活动期SLE方面均与抗dsDNA/C3抗体相当。在68例配对肾活检的患者中，增殖型和非增殖型狼疮性肾炎患者的尿中这些蛋白水平没有显著差异。尿CXCL4和VCAM-1与组织学活动评分显著相关，尿血管抑素与蛋白尿显著相关。尿Angiostatin、CXCL4和VCAM-1是SLE，尤其是狼疮性肾炎的潜在生物标志物。有必要进行进一步的纵向研究，以阐明这些标志物在预测SLE患者肾功能不全和预后方面的表现。
The aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE). Patients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine. Receiver operating characteristic analysis was performed to obtain the best cutoff values to calculate the performance of these markers in differentiating the different groups of patients as compared to anti-double-stranded DNA (anti-dsDNA) and complement C3. Correlation between these urinary biomarkers and various renal parameters was also tested. Patients with SLE (n = 227; 80 with inactive SLE, 67 with active non-renal disease and 80 with active renal disease; 94% women; age 39.2 ± 13.8 years) and 53 controls (96% women) were studied. All were ethnic Chinese. Urinary angiostatin, CXCL4 and VCAM-1 (normalized for creatinine) were significantly higher in patients with active renal disease than in patients with active non-renal disease, patients with inactive SLE and controls. These markers correlated significantly with total SLE disease activity index (SLEDAI) and renal SLEDAI scores, and with the urinary protein-to-creatinine ratio. Urine angiostatin exhibited higher specificity and sensitivity in differentiating active renal from active non-renal SLE (area under the curve (AUC) 0.87) than serum anti-dsDNA/C3. Urine CXCL4 (AUC 0.64) and VCAM-1 (AUC 0.73), on the other hand, performed similarly to anti-dsDNA/C3. All three markers performed comparably to anti-dsDNA/C3 in distinguishing active from inactive SLE. In a subgroup of 68 patients with paired renal biopsy, the urinary levels of these proteins did not differ significantly between the proliferative and non-proliferative types of lupus nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic activity score, and urinary angiostatin correlated significantly with proteinuria in this subgroup. Urinary angiostatin, CXCL4 and VCAM-1 are potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal studies are necessary to delineate the performance of these markers in predicting renal flares and prognosis in SLE patients.
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影响因子：
2.2
作者：
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作者：
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通讯作者：
Mok, C. C.