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系统性红斑狼疮中循环微粒子亚群受疾病活动度影响。

Circulating microparticle subpopulations in systemic lupus erythematosus are affected by disease activity.

作者信息

López Patricia, Rodríguez-Carrio Javier, Martínez-Zapico Aleida, Caminal-Montero Luis, Suárez Ana

机构信息

Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain.

Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain.

出版信息

Int J Cardiol. 2017 Jun 1;236:138-144. doi: 10.1016/j.ijcard.2017.02.107. Epub 2017 Mar 1.

DOI:10.1016/j.ijcard.2017.02.107
PMID:28279502
Abstract

BACKGROUND

Immune cells under chronic inflammation shed microparticles (MPs) that could fuel the inflammatory responses and atherosclerosis typically presented in systemic lupus erythematosus (SLE). This study analyzes total and subset-specific MPs from SLE patients and their possible influence on clinical features, leukocyte activation and serum cytokines.

METHODS

Total MPs and those derived from platelets, endothelial cells, monocytes, granulocytes and T-cells were quantified in plasma of 106 SLE patients and 33 healthy controls by flow cytometry. MP amounts were analyzed according to clinical manifestations, blood leukocyte populations and circulating cytokines (IFNα, TNFα, IL-10, BLyS, IL-17, IL-1β, CXCL10, CCL-2, CCL3, leptin). Finally, the in vitro effect of SLE-isolated MPs on the leukocyte activation status was analyzed.

RESULTS

Total circulating MPs in SLE patients were related to increased disease duration and the presence of cardiovascular disease. Furthermore, patients displayed increased counts of MPs from platelets, monocytes and T-lymphocytes, especially in SLE patients with disease activity or with TNFα-profile. Accordingly, MPs were associated with increased expression of activation markers in blood T-cells and monocytes. Finally, analyses propose a role of glucocorticoids in MPs generation and leukocyte activation since both fresh and cultured T-cells under this treatment presented higher IL-10 and CD25 production.

CONCLUSIONS

The altered profile of subset-specific SLE-MPs was influenced by the disease activity and altered status of leukocyte native cells, also associated with a TNFα-profile.

TRANSLATIONAL RESULTS

SLE patients, especially those with disease activity, displayed increased counts of MPs derived from platelets, monocytes and T-lymphocytes, which were more frequently found in TNFα-type patients. The origin of such SLE-MP subsets seems to be related to the over-activated status of T-cells and monocytes characteristic of these patients. Ex vivo and in vitro analyses propose a role of glucocorticoids in the generation of circulating MPs and leukocyte activation in SLE patients.

摘要

背景

慢性炎症状态下的免疫细胞会释放微颗粒(MPs),这些微颗粒可能会加剧炎症反应,并引发系统性红斑狼疮(SLE)中常见的动脉粥样硬化。本研究分析了SLE患者的总微颗粒和特定亚群微颗粒,以及它们对临床特征、白细胞活化和血清细胞因子的可能影响。

方法

通过流式细胞术对106例SLE患者和33例健康对照者血浆中的总微颗粒以及源自血小板、内皮细胞、单核细胞、粒细胞和T细胞的微颗粒进行定量。根据临床表现、血液白细胞群体和循环细胞因子(IFNα、TNFα、IL-10、BLyS、IL-17、IL-1β、CXCL10、CCL-2、CCL3、瘦素)分析微颗粒数量。最后,分析了SLE分离出的微颗粒对白细胞活化状态的体外影响。

结果

SLE患者循环中的总微颗粒与疾病持续时间延长和心血管疾病的存在有关。此外,患者血小板、单核细胞和T淋巴细胞来源的微颗粒数量增加,尤其是在疾病活动期或具有TNFα特征的SLE患者中。相应地,微颗粒与血液T细胞和单核细胞中活化标志物的表达增加有关。最后,分析表明糖皮质激素在微颗粒生成和白细胞活化中起作用,因为在此治疗下新鲜和培养的T细胞均呈现较高的IL-10和CD25产生。

结论

特定亚群的SLE微颗粒谱改变受疾病活动度和白细胞天然细胞状态改变的影响,也与TNFα特征有关。

转化结果

SLE患者,尤其是疾病活动期患者,血小板、单核细胞和T淋巴细胞来源的微颗粒数量增加,在TNFα型患者中更常见。这种SLE微颗粒亚群的来源似乎与这些患者特征性的T细胞和单核细胞过度活化状态有关。体外和体内分析表明糖皮质激素在SLE患者循环微颗粒的生成和白细胞活化中起作用。

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