Department of Emergency Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS One. 2020 Oct 27;15(10):e0240942. doi: 10.1371/journal.pone.0240942. eCollection 2020.
Given the urgent need for non-invasive biomarkers of LN, we aim to identify novel urinary biomarkers that facilitate diagnosis, assessment of disease activity and prediction of treatment response in a retrospective SLE cohort. A total of 154 SLE patients and 55 healthy controls were enrolled, among whom 73 were active LN patients. We measured renal activity by renal SLEDAI. The treatment response of the active LN patients who finished 6-month induction therapy was assessed based on the American College of Rheumatology response criteria. The expression levels of 10 urinary biomarkers (UBMs): β2-MG, calbindin D, cystatin C, IL-18, KIM-1, MCP-1, nephrin, NGAL, VCAM-1, and VDBP were tested using Luminex high-throughput proteomics technology. All but urinary nephrin levels were significantly increased in active LN compared to healthy controls. uCystatinC, uMCP-1, uKIM-1 levels were significantly higher in active LN group compared to inactive LN group. Correlation analysis revealed positive correlation between uCystatinC, uKIM-1, uMCP-1, uNGAL, uVDBP and RSLEDAI score. In renal pathology, uCystatinC, uKIM-1, uVCAM-1, and uVDBP positively correlated with activity index (AI) while uVCAM-1 positively correlated with chronicity index (CI). Moreover, the combination of uVCAM-1, uCystatinC, uKIM-1 discriminated proliferative LN from membranous LN with an AUC of 0.80 (95%CI: 0.69-0.90). Most importantly, baseline uNGAL demonstrated good prediction ability to discriminate responders from non-responders in active LN patients after 6-month induction therapy. Using a multiplex bead technique, we have identified the combination of uVCAM-1, uCystatinC, uKIM-1 as a biomarker panel to reflect renal pathology and NGAL as a promising urinary biomarker to both reflect disease activity and predict treatment response.
鉴于对 LN 无创生物标志物的迫切需求,我们旨在通过回顾性 SLE 队列,确定有助于诊断、评估疾病活动度和预测治疗反应的新型尿生物标志物。共纳入 154 例 SLE 患者和 55 例健康对照者,其中 73 例为活动期 LN 患者。我们通过肾脏 SLEDAI 评估肾脏活动度。根据美国风湿病学会反应标准,评估完成 6 个月诱导治疗的活动期 LN 患者的治疗反应。使用 Luminex 高通量蛋白质组学技术检测 10 种尿生物标志物 (UBM) 的表达水平:β2-MG、钙结合蛋白 D、胱抑素 C、IL-18、KIM-1、MCP-1、nephrin、NGAL、VCAM-1 和 VDBP。与健康对照组相比,活动期 LN 患者的所有 UBM 水平(除尿 nephrin 外)均显著升高。与非活动期 LN 组相比,活动期 LN 组 uCystatinC、uMCP-1、uKIM-1 水平显著升高。相关性分析显示,uCystatinC、uKIM-1、uMCP-1、uNGAL、uVDBP 与 RSLEDAI 评分呈正相关。在肾脏病理方面,uCystatinC、uKIM-1、uVCAM-1 和 uVDBP 与活动指数(AI)呈正相关,而 uVCAM-1 与慢性指数(CI)呈正相关。此外,uVCAM-1、uCystatinC、uKIM-1 的组合可区分增生性 LN 与膜性 LN,AUC 为 0.80(95%CI:0.69-0.90)。最重要的是,基线 uNGAL 显示出良好的预测能力,可区分 6 个月诱导治疗后活动期 LN 患者的应答者和非应答者。使用多指标珠技术,我们确定了 uVCAM-1、uCystatinC、uKIM-1 的组合作为反映肾脏病理的生物标志物组合,而 NGAL 作为一种有前途的尿生物标志物,可同时反映疾病活动度并预测治疗反应。