Table_1_Urine SERPINC1/ORM1 as biomarkers for early detection of lupus nephritis in MRL-lpr mice.docx

BackgroundTo evaluate the usefulness of urine SERPINC1 and ORM1 as biomarkers for early detection of lupus nephritis (LN).
MethodsUsing proteomics, we screened for potential urine biomarkers that differentiate LN from systemic lupus erythematosus (SLE) patients without nephritis. In addition, urine levels of target biomarkers were measured by ELISA in 13- and 23-week-old MRL-lpr (murine model for LN) and MRL/MpJ mice. Histological analysis was also performed on the kidneys of 23-week-old mice.
ResultsUrine SERPINC1 and ORM1 were elevated in SLE patients with newly diagnosed LN compared with SLE patients without LN (SERPINC1, AUC=.892, P<.001; ORM1, AUC=.886, P<.001). Levels of urine SERPINC1 and ORM1 were also significantly higher in MRL-lpr mice than in MRL/MpJ mice at 13 and 23 weeks (SERPINC1: p<.01 and p<.001 at 13 and 23 weeks, respectively; ORM1: p<.01 at 13 and 23 weeks). In contrast, a significant difference in urine albumin between the two groups was only observed at 23 weeks (p<.001) not at 13 weeks (p=.83). Regarding the kidney pathology of MPL-lpr mice, urine ORM1 and urine albumin, but not urine SERPINC1, were positively correlated with the activity index (ORM1, rho =.879, p<.001; albumin, rho =.807, p=.003) and chronicity index (ORM1, rho =.947, p<.001; albumin, rho =.869, p<.001).
ConclusionWe propose that urine SERPINC1 and ORM1 are novel biomarkers for early LN.

背景：为评估尿液SERPINC1与ORM1作为狼疮肾炎（lupus nephritis, LN）早期检测生物标志物的应用价值。
方法：本研究借助蛋白质组学（proteomics）技术，筛选可区分狼疮肾炎患者与无肾炎表现的系统性红斑狼疮（systemic lupus erythematosus, SLE）患者的潜在尿液生物标志物。此外，采用酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）检测13周龄与23周龄的MRL-lpr狼疮肾炎小鼠模型及MRL/MpJ小鼠的尿液靶标标志物水平。同时对23周龄小鼠的肾脏组织开展组织病理学分析。
结果：相较于无肾炎的SLE患者，初诊LN患者的尿液SERPINC1与ORM1水平显著升高（SERPINC1：曲线下面积（Area Under the Curve, AUC）=0.892，P<0.001；ORM1：AUC=0.886，P<0.001）。在13周龄与23周龄时，MRL-lpr小鼠的尿液SERPINC1与ORM1水平均显著高于MRL/MpJ小鼠（SERPINC1：13周龄时P<0.01，23周龄时P<0.001；ORM1：13周龄与23周龄时均P<0.01）。与之相对，两组小鼠尿液白蛋白水平仅在23周龄时存在显著差异（P<0.001），13周龄时无统计学差异（P=0.83）。针对MRL-lpr小鼠的肾脏病理分析结果显示，尿液ORM1与尿液白蛋白水平与肾脏病理活动指数及慢性指数均呈正相关，而尿液SERPINC1则无此相关性：其中ORM1与活动指数的斯皮尔曼相关系数rho=0.879，P<0.001；与慢性指数rho=0.947，P<0.001；白蛋白与活动指数rho=0.807，P=0.003；与慢性指数rho=0.869，P<0.001。
结论：本研究提示尿液SERPINC1与ORM1可作为狼疮肾炎早期检测的新型生物标志物。