Bergkamp S C, Wahadat M J, Salah A, Kuijpers T W, Smith V, Tas S W, van den Berg J M, Kamphuis S, Schonenberg-Meinema D
Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centres (AUMC), University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Department of Paediatric Rheumatology, Sophia Children's Hospital, Erasmus University Medical Centre, Rotterdam, The Netherlands.
J Inflamm (Lond). 2023 May 16;20(1):18. doi: 10.1186/s12950-023-00342-1.
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.
鉴于内皮细胞功能失调在系统性红斑狼疮（SLE）患者过早发生动脉粥样硬化中起主要作用，对参与SLE且与疾病活动相关的内皮细胞（EC）标志物进行系统的文献综述和荟萃分析。
检索词输入Embase、MEDLINE、Web of Science、Google Scholar和Cochrane数据库。纳入标准为：1）2000年后发表的报告SLE患者（根据ACR/SLICC标准诊断）血清和/或血浆中EC标志物测量结果的研究；2）英文同行评审文章；3）疾病活动度测量。进行荟萃分析计算时，使用了伊拉斯姆斯管理研究所（ERIM）的Meta-Essentials工具。仅纳入那些：1）至少在两篇文章中被报道，且2）报道了EC标志物测量水平与疾病活动度之间的相关系数（即斯皮尔曼等级相关系数或皮尔逊相关系数）的EC标志物。荟萃分析采用固定效应模型。
从2133条检索结果中，筛选出123篇符合条件的文章。确定的与SLE相关的内皮标志物涉及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。对主要横断面研究的荟萃分析显示，以下内皮标志物的标志物水平与疾病活动度之间存在显著关联：五聚体蛋白-3、血栓调节蛋白、血管内皮生长因子（VEGF）、血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）、干扰素诱导蛋白10（IP-10）和单核细胞趋化蛋白-1（MCP-1）。与疾病活动度无关联的内皮标志物功能失调包括：血管生成素-2、血管性血友病因子（vWF）、P-选择素、肿瘤坏死因子样弱凋亡诱导因子（TWEAK）和E-选择素。
我们提供了一份关于SLE中内皮标志物功能失调的完整文献综述，涵盖了广泛的不同内皮细胞功能。SLE诱导的内皮标志物失调与疾病活动度有关，但也有无关联的情况。本研究在将内皮标志物作为SLE生物标志物这一复杂领域提供了一些清晰的认识。现在需要SLE中内皮标志物的纵向数据，以在揭示SLE患者过早动脉粥样硬化和心血管事件的病理生理学方面为我们提供更多指导。
