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首页> 外文期刊>Immunology Letters >Differential clearance mechanisms, neutrophil extracellular trap degradation and phagocytosis, are operative in systemic lupus erythematosus patients with distinct autoantibody specificities
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Differential clearance mechanisms, neutrophil extracellular trap degradation and phagocytosis, are operative in systemic lupus erythematosus patients with distinct autoantibody specificities

机译:差异清除机制,嗜中性粒细胞胞外陷阱降解和吞噬作用在具有独特自身抗体特异性的系统性红斑狼疮患者中有效

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Systemic lupus erythematosus (SLE) patients are generally presented with autoantibodies against either dsDNA or RNA-associated antigens (also known as extractable nuclear antigens, ENA) or both. However, the mechanisms and processes that lead to this distinctive autoantibody profile are not well understood. Defects in clearance mechanism i.e. phagocytosis may lead to enhanced microbial and cellular debris of immunogenic potential. In addition to defective phagocytosis, impaired neutrophil extracellular trap (NET) degradation has been recently reported in SLE patients. However, the extent to which both these clearance processes (NET-degradation and phagocytosis) are operative in serologically distinguished subsets of SLE patients is not established. Therefore, in this report, we evaluated NET-degradation and phagocytosis efficiency among SLE patients with different autoantibody specificities. SLE patients were classified into three subsets based on their autoantibody profile (anti-dsDNA, anti-ENA or both) as determined by ELISA. NET-degradation by SLE and control sera was assessed by sytox orange-based fluorescence assay. Neutrophil-mediated phagocytosis in the presence of SLE and control sera was determined by flowcytometry. The segregation of SLE patients revealed significant differences in NET-degradation and phagocytosis in SLE patients with autoantibodies against dsDNA and ENA. We report that NET-degradation efficiency was significantly impaired in SLE patients with anti-dsDNA autoantibodies and not in those with anti-ENA autoantibodies. In contrast to NET-degradation, neutrophil-mediated phagocytosis was impaired in all three subsets independent of autoantibody specificity. These observations suggest that varying clearance mechanisms are operative in SLE subsets with anti-dsDNA or anti-ENA autoantibodies. The results outlined in this manuscript also suggest that sub-grouping of SLE patients could be useful in delineating the molecular and pathological processes that are often missed when SLE patients are studied as a single group. Further, it will be imperative to propose that therapies targeted at improving NET clearance can be effective in anti-dsDNA(+) SLE patients. (C) 2015 Elsevier B.V. All rights reserved.
机译:系统性红斑狼疮(SLE)患者通常会出现针对dsDNA或RNA相关抗原(也称为可提取核抗原,ENA)或两者的自身抗体。但是,导致这种独特的自身抗体谱的机制和过程尚不十分清楚。清除机制的缺陷(即吞噬作用)可能会导致微生物和细胞碎屑具有潜在的免疫原性。除了吞噬功能缺陷外,最近还报道了SLE患者中性粒细胞胞外诱集细胞(NET)降解受损。然而,尚不清楚这些清除过程(NET降解和吞噬作用)在SLE患者的血清学上可区分的亚类中起作用的程度。因此,在本报告中,我们评估了具有不同自身抗体特异性的SLE患者的NET降解和吞噬效率。根据ELISA测定,SLE患者根据自身抗体谱(抗dsDNA,抗ENA或两者)分为三类。 SLE和对照血清的NET降解通过基于橙的荧光法进行评估。通过流式细胞术确定在SLE和对照血清存在下中性粒细胞介导的吞噬作用。 SLE患者的隔离显示,在具有针对dsDNA和ENA的自身抗体的SLE患者中,NET降解和吞噬作用存在显着差异。我们报告说,在具有抗dsDNA自身抗体的SLE患者中,而不是在具有抗ENA自身抗体的SLE患者中,NET降解效率显着降低。与NET降解相反,中性粒细胞介导的吞噬作用在所有三个亚组中均受到损害,而与自身抗体特异性无关。这些观察结果表明,在具有抗dsDNA或抗ENA自身抗体的SLE亚组中,不同的清除机制是有效的。该手稿中概述的结果还表明,SLE患者的亚组可能有助于勾勒出将SLE患者作为一个整体进行研究时常常遗漏的分子和病​​理过程。此外,必须提出针对提高NET清除率的疗法对抗dsDNA(+)SLE患者有效。 (C)2015 Elsevier B.V.保留所有权利。

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