风湿

狼疮自身抗体可加重血栓并发症的发生

作者:Le Minh G,et al. 译者:北医三院曹思愚 来源:中国风湿病公众论坛 日期:2018-03-14
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         【前沿进展】狼疮自身抗体可加重血栓并发症的发生

关键字:  自身抗体 | 血栓 

        摘要本文旨在探讨系统性红斑狼疮血栓并发症中血栓收缩可能的作用。使用一种新型的自动化方法,我们调查了51名SLE患者和60名健康献血者的血液凝块收缩的动力学。使用流式细胞术通过P-选择素和纤维蛋白原结合能力的表达来评估SLE患者中血小板的功能。 SLE患者的血栓收缩率和程度明显低于正常人,特别是血液中抗dsDNA抗体水平较高的患者。血小板收缩力降低与从SLE患者血液中分离的血小板对由凝血酶受体激活肽诱导的刺激的部分不应性相关。为了测试抗dsDNA自身抗体是否引起血小板的持续活化,以及细胞的衰竭和功能障碍,我们在凝血之前将来自SLE患者的纯化的外源抗dsDNA自身抗体加入到正常血液中。为了支持这一假设,抗体首先增强血块收缩,然后以时间依赖性的方式抑制它。重要的是,血块收缩参数与疾病严重程度的直接相关性表明,血管内凝块和血栓的致密性降低可能是SLE中的致病因素,其可能夸大血栓形成部位处的受损血流。综上所述,SLE自身抗体可影响血小板收缩能力,导致凝块和血栓体积缩小的能力下降,增加血管阻塞,加重SLE血栓并发症的发生,发展。

        附原文:The aim of this work was to examine a possible role ofclot contraction/retraction in thrombotic complications of systemic lupuserythematosus (SLE). Using a novel automated method, we investigated kineticsof clot contraction in the blood of 51 SLE patients and 60 healthy donors. Thefunctionality of platelets in the SLE patients was assessed using flowcytometry by expression of P-selectin and fibrinogen-binding capacity. The rateand degree of clot contraction were significantly reduced in SLE patientscompared to healthy subjects, especially in the patients with higher bloodlevels of anti-dsDNA antibodies. The reduced platelet contractility correlatedwith partial refractoriness of platelets isolated from the blood of SLEpatients to stimulation induced by the thrombin receptor activating peptide. Totest if the anti-dsDNA autoantibodies cause continuous platelet activation,followed by exhaustion and dysfunction of the cells, we added purifiedexogenous anti-dsDNA autoantibodies from SLE patients to normal blood beforeclotting. In support of this hypothesis, the antibodies first enhanced clotcontraction and then suppressed it in a time-dependent manner. Importantly, adirect correlation of clot contraction parameters with the disease severitysuggests that the reduced compactness of intravascular clots and thrombi couldbe a pathogenic factor in SLE that may exaggerate the impaired blood flow atthe site of thrombosis. In conclusion, autoantibodies in SLE can affectplatelet contractility, resulting in reduced ability of clots and thrombi to shrinkin volume, which increases vessel obstruction and may aggravate the course andoutcomes of thrombotic complications in SLE.

        引自:Le Minh G,Peshkova AD,Andrianova IA,et al.Impaired contraction of bloodclots as a novel prothrombotic mechanism in systemic lupus erythematosus. ClinSci (Lond), 2018 Jan 19;132(2):243-254. doi: 10.1042/CS20171510. Print 2018 Jan31.

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