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系统性红斑狼疮中循环微颗粒的独特特征及其与临床表现的关系。

Distinct features of circulating microparticles and their relationship to clinical manifestations in systemic lupus erythematosus.

作者信息

Nielsen Christoffer T, Østergaard Ole, Johnsen Christina, Jacobsen Søren, Heegaard Niels H H

机构信息

Statens Serum Institut, Copenhagen, Denmark.

出版信息

Arthritis Rheum. 2011 Oct;63(10):3067-77. doi: 10.1002/art.30499.

Abstract

OBJECTIVE

Characterization of the abundance, origin, and annexin V (AnxV)-binding capabilities of circulating microparticles (MPs) in SLE patients and healthy controls and to determine any associations with clinical parameters.

METHODS

Seventy unselected SLE patients and 29 sex- and age-matched healthy control subjects were included in the study. MPs were isolated from citrate-treated plasma and characterized by flow cytometry using AnxV or antibodies to platelet, leukocyte, or endothelial cell surface markers.

RESULTS

SLE patients had significantly increased concentrations of AnxV-nonbinding (AnxV-) MPs (P<0.0001), while the concentrations of total MPs (P=0.011) and AnxV-binding (AnxV+) MPs (P<0.0001) were decreased, as compared with controls. Based on flow cytometric characteristics, 2 subgroups of AnxV- MPs could be discerned: AnxV- cell-derived MPs (CDMPs) and AnxV- MPs of unknown nature (UNMPs). Both fractions were significantly increased in SLE patients (P=0.007 and P=0.0018, respectively). Platelet- and leukocyte-derived MPs were decreased in the SLE patients (P<0.0001), whereas no difference was observed for endothelial cell-derived MPs (P=0.14). The concentrations of AnxV- CDMPs correlated with the concentrations of endothelial cell-derived MPs, the disease activity score, active nephritis, hypertension, history of arterial thrombosis, and triglyceride levels (P<0.05 for all comparisons).

CONCLUSION

The concentrations and composition of MPs in SLE patients differ markedly from those in healthy subjects. Overall MP numbers were significantly decreased, but two distinct subpopulations of AnxV- MPs were significantly increased. These findings call for further characterization of MPs in SLE patients to elucidate their role in disease pathogenesis.

摘要

目的

对系统性红斑狼疮(SLE)患者和健康对照者循环微颗粒(MPs)的丰度、来源及膜联蛋白V(AnxV)结合能力进行表征,并确定其与临床参数的任何关联。

方法

本研究纳入了70例未经挑选的SLE患者和29例性别及年龄匹配的健康对照者。从枸橼酸盐处理的血浆中分离出MPs,并使用AnxV或针对血小板、白细胞或内皮细胞表面标志物的抗体通过流式细胞术进行表征。

结果

与对照组相比,SLE患者AnxV非结合性(AnxV-)MPs的浓度显著升高(P<0.0001),而总MPs(P=0.011)和AnxV结合性(AnxV+)MPs的浓度降低(P<0.0001)。基于流式细胞术特征,可识别出AnxV- MPs的两个亚组:AnxV-细胞衍生MPs(CDMPs)和性质不明的AnxV- MPs(UNMPs)。SLE患者的这两个组分均显著增加(分别为P=0.007和P=0.0018)。SLE患者中血小板和白细胞衍生的MPs减少(P<0.0001),而内皮细胞衍生的MPs未观察到差异(P=0.14)。AnxV- CDMPs的浓度与内皮细胞衍生的MPs浓度、疾病活动评分、活动性肾炎、高血压、动脉血栓形成病史和甘油三酯水平相关(所有比较P<0.05)。

结论

SLE患者MPs的浓度和组成与健康受试者明显不同。总体MP数量显著减少,但AnxV- MPs的两个不同亚群显著增加。这些发现需要对SLE患者的MPs进行进一步表征,以阐明它们在疾病发病机制中的作用。

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