Tydén Helena, Lood Christian, Gullstrand Birgitta, Nielsen Christoffer Tandrup, Heegaard Niels H H, Kahn Robin, Jönsen Andreas, Bengtsson Anders A
Department of Rheumatology, Clinical Sciences Lund, Lunds University, Lund, Sweden.
Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
RMD Open. 2017 Oct 25;3(2):e000508. doi: 10.1136/rmdopen-2017-000508. eCollection 2017.
Endothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial dysfunction and platelet activation. In this study, we investigated the interplay between endothelial dysfunction, platelets and type I IFN in SLE.
We enrolled 148 patients with SLE and 79 sex-matched and age-matched healthy controls (HCs). Type I IFN activity was assessed with a reporter cell assay and platelet activation by flow cytometry. Endothelial dysfunction was assessed using surrogate markers of endothelial activation, soluble vascular cell adhesion molecule-1 (sVCAM-1) and endothelial microparticles (EMPs), and finger plethysmograph to determine Reactive Hyperaemia Index (RHI).
In patients with SLE, type I IFN activity was associated with endothelial activation, measured by high sVCAM-1 (OR 1.68, p<0.01) and elevated EMPs (OR 1.40, p=0.03). Patients with SLE with high type I IFN activity had lower RHI than HCs (OR 2.61, p=0.04), indicating endothelial dysfunction.Deposition of complement factors on platelets, a measure of platelet activation, was seen in patients with endothelial dysfunction. High levels of sVCAM-1 were associated with increased deposition of C4d (OR 4.57, p<0.01) and C1q (OR 4.10, p=0.04) on platelets. High levels of EMPs were associated with C4d deposition on platelets (OR 3.64, p=0.03).
Endothelial dysfunction was associated with activation of platelets and the type I IFN system. We suggest that an interplay between the type I IFN system, injured endothelium and activated platelets may contribute to development of CVD in SLE.
内皮功能障碍可能与系统性红斑狼疮（SLE）中的心血管疾病（CVD）相关。I型干扰素（IFN）在SLE发病机制中起核心作用，并被认为可诱导内皮功能障碍和血小板活化。在本研究中，我们调查了SLE中内皮功能障碍、血小板与I型干扰素之间的相互作用。
我们纳入了148例SLE患者和79例性别及年龄匹配的健康对照（HC）。通过报告细胞测定评估I型干扰素活性，通过流式细胞术评估血小板活化。使用内皮活化的替代标志物、可溶性血管细胞粘附分子-1（sVCAM-1）和内皮微粒（EMP）以及手指体积描记法来评估内皮功能障碍，以确定反应性充血指数（RHI）。
在SLE患者中，I型干扰素活性与通过高sVCAM-1（比值比[OR] 1.68，p<0.01）和升高的EMP（OR 1.40，p = 0.03）测量的内皮活化相关。I型干扰素活性高的SLE患者的RHI低于HC（OR 2.61，p = 0.04），表明存在内皮功能障碍。在内皮功能障碍的患者中观察到补体因子在血小板上的沉积，这是血小板活化的一种测量指标。高水平的sVCAM-1与血小板上C4d沉积增加（OR 4.57，p<0.01）和C1q沉积增加（OR 4.10，p = 0.04）相关。高水平的EMP与血小板上C4d沉积相关（OR 3.64，p = 0.03）。
内皮功能障碍与血小板活化和I型干扰素系统相关。我们认为I型干扰素系统、受损内皮和活化血小板之间的相互作用可能促成SLE中CVD的发展。
