Hospital Quironsalud del Vallés, Internal Medicine Department, 08202 Sabadell, Spain.
Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Rheumatology research group, Lupus Unit, 08035 Barcelona, Spain.
Int J Mol Sci. 2019 Sep 17;20(18):4601. doi: 10.3390/ijms20184601.
At present, Lupus Nephritis (LN) is still awaiting a biomarker to better monitor disease activity, guide clinical treatment, and predict a patient's long-term outcome. In the last decade, novel biomarkers have been identified to monitor the disease, but none have been incorporated into clinical practice. The transmembrane receptor neuropilin-1 (NRP-1) is highly expressed by mesangial cells and its genetic deletion results in proteinuric disease and glomerulosclerosis. NRP-1 is increased in kidney biopsies of LN. In this work we were interested in determining whether urinary NRP-1 levels could be a biomarker of clinical response in LN. Our results show that patients with active LN have increased levels of urinary NRP-1. When patients were divided according to clinical response, responders displayed higher urinary and tissue NRP-1 levels at the time of renal biopsy. Areas under the receiver operating characteristic curve, comparing baseline creatinine, proteinuria, urinary NRP-1, and VEGFA protein levels, showed NRP-1 to be an independent predictor for clinical response. In addition, in vitro studies suggest that NRP-1could promote renal recovery through endothelial proliferation and migration, mesangial migration and local T cell cytotoxicity. Based on these results, NRP-1 may be used as an early prognostic biomarker in LN.
目前,狼疮性肾炎(LN)仍在等待一种生物标志物,以更好地监测疾病活动、指导临床治疗并预测患者的长期预后。在过去十年中,已经确定了一些新的生物标志物来监测该疾病,但没有一种被纳入临床实践。跨膜受体神经纤毛蛋白-1(NRP-1)在系膜细胞中高度表达,其基因缺失会导致蛋白尿疾病和肾小球硬化。在 LN 的肾活检中,NRP-1 增加。在这项工作中,我们有兴趣确定尿 NRP-1 水平是否可以作为 LN 临床反应的生物标志物。我们的结果表明,活动期 LN 患者的尿 NRP-1 水平升高。当根据临床反应对患者进行分组时, responder 患者在肾活检时的尿和组织 NRP-1 水平更高。比较基线肌酐、蛋白尿、尿 NRP-1 和 VEGFA 蛋白水平的受试者工作特征曲线下面积显示,NRP-1 是临床反应的独立预测因子。此外,体外研究表明,NRP-1 可通过内皮细胞增殖和迁移、系膜细胞迁移和局部 T 细胞细胞毒性促进肾脏恢复。基于这些结果,NRP-1 可作为 LN 的早期预后生物标志物。