Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University.
J Atheroscler Thromb. 2019 Jun 1;26(6):538-546. doi: 10.5551/jat.46284. Epub 2018 Nov 15.
Idiopathic membranous nephropathy (IMN) is an immune-mediated inflammatory disease characterized by a high risk of thromboembolic complications. Microparticles (MPs), a type of extracellular vesicles, have procoagulant properties, especially when they display tissue factor (TF). This study aimed to investigate whether circulating TF-positive MPs contributed to the hypercoagulable state in patients with IMN.
Twenty adult IMN patients and fourteen healthy subjects were included in the study. The basic indexes of a routine biochemical examination and coagulative function were determined. The plasma levels of MPs were detected by flow cytometry, and TF activity of MPs was examined using an assay kit. The plasma levels of lipopolysaccharide (LPS) were measured by an enzyme-linked immunosorbent assay.
Total circulating MPs were not increased in patients with IMN compared with healthy controls. Circulating CD14/TFMPs were significantly increased in IMN patients, but this achieved significance was not observed in CD41/TFMPs between the two groups. Interestingly, the circulating TF-positive MPs were increased significantly. Plasma MPs TF assays revealed high procoagulant activity, which was positively associated with the D-dimer level in IMN. In addition, circulating LPS in IMN patients were significantly higher than those in the controls. Furthermore, after two hours' incubation with healthy whole blood, LPS enhanced the release of circulating TF-positive MPs and the TF activity of MPs.
Increased circulating LPS may mediate the release of monocyte-derived TF-positive MPs, which further contributes to the hypercoagulable state in IMN patients. These findings provide an additional mechanism by which patients with IMN have a higher risk of thromboembolic complication.
特发性膜性肾病（IMN）是一种免疫介导的炎症性疾病，其特征是血栓栓塞并发症的风险较高。微粒（MPs）是一种细胞外囊泡，具有促凝特性，尤其是当它们显示组织因子（TF）时。本研究旨在探讨循环 TF 阳性 MPs 是否导致 IMN 患者的高凝状态。
本研究纳入了 20 名成年 IMN 患者和 14 名健康对照者。测定常规生化检查和凝血功能的基本指标。采用流式细胞术检测 MPs 的血浆水平，采用试剂盒检测 MPs 的 TF 活性。采用酶联免疫吸附试验测定血浆中脂多糖（LPS）的水平。
与健康对照组相比，IMN 患者的总循环 MPs 没有增加。IMN 患者的循环 CD14/TFMPs 显著增加，但两组间的 CD41/TFMPs 没有观察到这种变化。有趣的是，循环 TF 阳性 MPs 明显增加。血浆 MPs TF 测定显示高促凝活性，与 IMN 患者的 D-二聚体水平呈正相关。此外，IMN 患者的循环 LPS 明显高于对照组。此外，在与健康全血孵育两小时后，LPS 增强了循环 TF 阳性 MPs 的释放和 MPs 的 TF 活性。
循环 LPS 的增加可能介导单核细胞来源的 TF 阳性 MPs 的释放，进而导致 IMN 患者的高凝状态。这些发现为 IMN 患者发生血栓栓塞并发症风险较高提供了另一种机制。
