To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman’s rank or Pearson’s) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used. From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin. We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.

中文翻译：

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系统性红斑狼疮中失调的内皮细胞标志物：系统回顾和荟萃分析

对与系统性红斑狼疮 (SLE) 相关的内皮细胞 (EC) 标志物进行系统的文献综述和荟萃分析. 搜索词被输入到 Embase、MEDLINE、Web of Science、Google Scholar 和 Cochrane。纳入标准是 1) 2000 年之后发表的研究，报告了 SLE 患者（根据 ACR/SLICC 标准诊断）血清和/或血浆中 EC 标志物的测量，2) 英文同行评议文章，以及 3) 疾病活动测量。对于元分析计算，使用了 Erasmus Research Institute and of Management (ERIM) 的 Meta-Essentials 工具。只有那些 EC 标记，其中 1) 至少在两篇文章中有报道，并且 2) 报道了 EC 标记物测量水平与疾病活动度之间的相关系数（即 Spearman 等级或 Pearson 等级）。对于荟萃分析，使用固定效应模型。从 2133 次点击中，选择了 123 篇符合条件的文章。已鉴定的 SLE 相关内皮标志物参与 EC 激活、EC 凋亡、血管生成紊乱、血管张力控制缺陷、免疫失调和凝血病。主要横断面研究的荟萃分析显示，以下内皮标记物的标记物水平与疾病活动之间存在显着关联：Pentraxin-3、血栓调节蛋白、VEGF、VCAM-1、ICAM-1、IP-10 和 MCP-1。与疾病活动无关的失调 EC 标志物是：Angiopoeitin-2、vWF、P-Selectin、TWEAK 和 E-Selectin。我们提供了 SLE 中失调的 EC 标志物的完整文献综述，包括各种不同的 EC 功能。SLE 诱导的 EC 标志物失调与疾病活动有关，但也与疾病活动无关。这项研究在 EC 标志物作为 SLE 生物标志物的重要复杂领域提供了一些清晰度。现在需要 SLE 中 EC 标志物的纵向数据来指导我们更多地阐明 SLE 患者过早动脉粥样硬化和心血管事件的病理生理学。