International validation of a urinary biomarker panel for identification of active lupus nephritis in children.
International validation of a urinary biomarker panel for identification of active lupus nephritis in children.
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DOI：
10.1007/s00467-016-3485-3
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发表时间：
2017-02
期刊：
影响因子：
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通讯作者：
Beresford MW
中科院分区：
文献类型：
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作者：
Smith EM;Jorgensen AL;Midgley A;Oni L;Goilav B;Putterman C;Wahezi D;Rubinstein T;Ekdawy D;Corkhill R;Jones CA;Marks SD;Newland P;Pilkington C;Tullus K;Beresford MW
传统的标志物的青少年发病系统性红斑狼疮（JSLE）疾病活动不能充分识别狼疮性肾炎（LN）。虽然个别新的尿液生物标志物是很好的检测LN耀斑，生物标志物面板可以提高诊断的准确性。本研究的目的是评估生物标志物小组在两个国际JSLE队列中识别活动性LN的性能。新的尿生物标志物，即血管细胞粘附分子-1（VCAM-1）、单核细胞趋化蛋白1（MCP-1）、脂质运载蛋白样前列腺素D合酶（LPGDS）、转铁蛋白（TF）、血浆铜蓝蛋白、α-1-酸性糖蛋白（AGP）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL），在包括英国JSLE队列研究（队列1）参与者的横断面研究中进行量化，并在爱因斯坦狼疮队列（队列2）中进行验证。使用二元逻辑回归建模和受试者工作特征曲线分析[曲线下面积（AUC）]来鉴定和评估生物标志物的组合以获得诊断准确性。两个队列共招募了91名JSLE患者，其中31名（34%）患有活动性LN，60名（66%）没有LN。在两个队列中，活动性LN患者的尿AGP、铜蓝蛋白、VCAM-1、MCP-1和LPGDS水平显著高于非LN患者[所有校正p值（p c）< 0.05]。队列2中患者组间的尿TF也存在差异（p c = 0.001）。在队列1中，最佳生物标志物组包括AGP、血浆铜蓝蛋白、LPGDS和TF（活动性LN鉴定的AUC 0.920）。这些结果在队列2中得到验证，相同的标志物产生了最佳尿液生物标志物组（AUC 0.991）。在两个国际JSLE队列中，尿AGP、铜蓝蛋白、LPGDS和TF表现出“极好”的准确识别儿童活动性LN的能力。本文的在线版本（doi：10.1007/s 00467 -016-3485-3）包含补充材料，可供授权用户使用。
Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts. Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy. A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (p c) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (p c = 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991). In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an ‘excellent’ ability for accurately identifying active LN in children. The online version of this article (doi:10.1007/s00467-016-3485-3) contains supplementary material, which is available to authorized users.