The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.
Mediators Inflamm. 2022 Apr 13;2022:8447675. doi: 10.1155/2022/8447675. eCollection 2022.
Identifying new markers of juvenile systemic lupus erythematosus (JSLE) is critical event to predict patient stratification and prognosis. The aim of the present study is to analyze alteration of urinary protein expression and screen potential valuable biomarkers in juvenile systemic lupus erythematosus (JSLE).
The urine was collected from the patients with or without JSLE and detected by mass spectrometry to analyze proteomic changes. ELISA was used to verify the Vitronectin (VTN) changes in a new set of patients. The clinical correlation was performed to analyze between VTN and clinical pathological parameters. WB and ELISA were used to analyze VTN-mediated cell pyroptosis.
Herein, we have identified a group of 105 differentially expressed proteins with ≥1.3-fold upregulation or ≤0.77-fold downregulation in JSLE patients. These proteins were involved in several important biological processes, including acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation through Gene Ontology and functional enrichment analysis. Interestingly, urinary ephrin type-A receptor 4 (EPHA4) and VTN were significantly reduced in both inactive and active JSLE patients, and VTN treatment in THP-1 derived macrophages led to a significant increased cell pyroptosis by activation of Nod-like receptor family protein 3 (NLRP3) inflammasomes, resulting in caspase-1 activation, cleaved gasdermin D (GSDMD), and IL-18 secretion. Most importantly, the urinary VTN was also linearly correlated with clinical characteristics of JSLE, implying that VTN could be a specific diagnostic biomarker to distinguish inactive and active JSLE.
This study provided a novel role of VTN in pyroptosis in JSLE through the urinary proteomic profile for JSLE, which could be a nonintrusive monitoring strategy in clinical diagnosis.
确定幼年系统性红斑狼疮（JSLE）的新标志物对于预测患者分层和预后至关重要。本研究旨在分析尿蛋白表达的变化，并筛选幼年系统性红斑狼疮（JSLE）中的潜在有价值的生物标志物。
收集有或无 JSLE 的患者的尿液，通过质谱分析进行蛋白质组学分析。ELISA 用于验证 Vitronectin（VTN）在新患者组中的变化。进行临床相关性分析，以分析 VTN 与临床病理参数之间的关系。WB 和 ELISA 用于分析 VTN 介导的细胞焦亡。
在此，我们鉴定了一组在 JSLE 患者中表达上调≥1.3 倍或下调≤0.77 倍的 105 种差异表达蛋白。通过基因本体论和功能富集分析，这些蛋白参与了几个重要的生物学过程，包括急性期炎症反应、补体激活、止血和免疫系统调节。有趣的是，在无活动和活动 JSLE 患者中，尿 Ephrin 型-A 受体 4（EPHA4）和 VTN 均显著降低，而 VTN 处理 THP-1 衍生的巨噬细胞导致 NLRP3 炎性体的显著激活，导致 caspase-1 激活、裂解的 Gasdermin D（GSDMD）和 IL-18 分泌，从而导致细胞焦亡显著增加。最重要的是，尿 VTN 与 JSLE 的临床特征呈线性相关，表明 VTN 可能是区分无活动和活动 JSLE 的特异性诊断生物标志物。
通过 JSLE 的尿液蛋白质组学分析，本研究为 VTN 在 JSLE 中的细胞焦亡中提供了新的作用机制，这可能是临床诊断中的一种非侵入性监测策略。
