Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
Rheumatology (Oxford). 2012 Oct;51(10):1775-84. doi: 10.1093/rheumatology/kes152. Epub 2012 Jun 29.
The aim of this study was to investigate the endothelial progenitor cell population in SLE and early RA patients and its potential relationships with disease features and cytokine serum levels.
Endothelial progenitor cells (EPCs), mature EPCs (mEPCs) and endothelial cells (ECs) were measured in peripheral blood samples from 83 SLE and 85 early RA patients and 39 healthy controls by flow cytometry on the basis of CD34, VEGF receptor 2 and CD133 expression. Serum levels of IL-1β, IL-6, IL-8, IL-17, VEGF-A, IFN-α, TGF-β and GM-CSF were quantified by immunoassays. Clinical and immunological data were obtained by reviewing clinical histories.
Circulating EPCs were increased in SLE but not in early RA patients associated with an enhanced CD34(+) bone marrow-progenitor cell release but unrelated to disease features. The amount of mEPCs, however, was significantly higher in SLE patients presenting anti-SSA/SSB antibodies and/or malar rash, whereas the presence of specific autoantibodies was associated with EC counts in early RA and SLE patients. As expected, most cytokines tested were altered in both diseases but, interestingly, IFN-α levels, and to a lesser extent IL-6 and IL-1β, were associated with CD133 loss and increased mEPC number, whereas VEGF and TGF-β seem to exert an opposite effect.
Our results show that high IFN-α levels and/or the presence of disease-specific antibodies may identify a group of SLE patients with increased mEPC and EC counts, and consequently probably defective endothelial repair, thus supporting their use as surrogate biomarkers of endothelial damage and high cardiovascular risk.
本研究旨在探讨系统性红斑狼疮(SLE)和早期类风湿关节炎(RA)患者的内皮祖细胞(EPC)群体及其与疾病特征和细胞因子血清水平的潜在关系。
采用流式细胞术,根据 CD34、VEGF 受体 2 和 CD133 的表达,检测 83 例 SLE 和 85 例早期 RA 患者及 39 例健康对照者外周血样本中的 EPC、成熟 EPC(mEPC)和内皮细胞(EC)。采用免疫分析法检测血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-17(IL-17)、血管内皮生长因子-A(VEGF-A)、干扰素-α(IFN-α)、转化生长因子-β(TGF-β)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的水平。通过查阅病历获取临床和免疫数据。
SLE 患者循环 EPC 增加,但早期 RA 患者无此变化,这与骨髓祖细胞释放增强有关,但与疾病特征无关。然而,SLE 患者中 mEPC 数量明显增加,这些患者表现出抗 SSA/SSB 抗体和/或蝶形皮疹,而特定自身抗体的存在与早期 RA 和 SLE 患者的 EC 计数有关。不出所料,两种疾病中大多数细胞因子均发生改变,但有趣的是,IFN-α 水平,以及在较小程度上的 IL-6 和 IL-1β,与 CD133 缺失和 mEPC 数量增加有关,而 VEGF 和 TGF-β 似乎具有相反的作用。
我们的结果表明,高 IFN-α 水平和/或存在疾病特异性抗体可能会识别出一组 SLE 患者,这些患者的 mEPC 和 EC 计数增加,因此内皮修复可能受损,从而支持它们作为内皮损伤和高心血管风险的替代生物标志物。