Systemic lupus erythematosus (SLE) is associated with a high risk of venous and arterial thrombosis, not necessarily associated with prothrombotic antiphospholipid antibodies (Abs). Alternatively, thrombosis may be due to an increased titer of anti-dsDNA Abs that presumably promote thrombosis via direct platelet activation. Here, we investigated effects of purified anti-dsDNA Abs from the blood of SLE patients, alone or in a complex with dsDNA, on isolated normal human platelets. We showed that anti-dsDNA Abs and anti-dsDNA Ab/dsDNA complexes induced strong platelet activation assessed by enhanced P-selectin expression and dramatic morphological and ultrastructural changes. Electron microscopy revealed a significantly higher percentage of platelets that lost their discoid shape, formed multiple filopodia and had a shrunken body when treated with anti-dsDNA Abs or anti-dsDNA Ab/dsDNA complexes compared with control samples. In addition, these platelets activated with anti-dsDNA Ab/dsDNA complexes typically contained a reduced number of secretory α-granules that grouped in the middle and often merged into a solid electron dense area. Many activated platelets released plasma membrane-derived microvesicles and/or fell apart into subcellular cytoplasmic fragments. Confocal microscopy revealed that platelets treated with anti-dsDNA Ab/dsDNA complex had a heterogeneous distribution of septin2 compared with the homogeneous distribution in control platelets. Structural perturbations were concomitant with mitochondrial depolarization and a decreased content of platelet ATP, indicating energetic exhaustion. Most of the biochemical and morphological changes in platelets induced by anti-dsDNA Abs and anti-dsDNA Ab/dsDNA complexes were prevented by pre-treatment with a monoclonal mAb against FcγRIIA. The aggregate of data indicates that anti-dsDNA Abs alone or in a complex with dsDNA strongly affect platelets via the FcγRIIA receptor. The immune activation of platelets with antinuclear Abs may comprise a prothrombotic mechanism underlying a high risk of thrombotic complications in patients with SLE.

中文翻译：

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在系统性红斑狼疮中，抗dsDNA抗体可通过直接激活血小板来促进血栓形成。

系统性红斑狼疮（SLE）与静脉和动脉血栓形成的高风险相关，不一定与血栓形成前的抗磷脂抗体（Abs）相关。或者，血栓形成可能是由于抗dsDNA Abs滴度增加，可能是通过直接血小板活化而促进了血栓形成。在这里，我们调查了单独或与dsDNA结合的SLE患者血液中纯化的抗dsDNA Abs对分离的正常人血小板的作用。我们显示抗dsDNA Abs和抗dsDNA Ab / dsDNA复合物诱导增强的P-选择素表达和显着的形态学和超微结构变化评估的强烈的血小板活化。电子显微镜检查显示，失去盘状形状的血小板比例明显更高，与对照样品相比，用抗dsDNA Abs或抗dsDNA Ab / dsDNA复合物处理时，形成多发性丝状伪足并具有收缩的身体。此外，这些被抗dsDNA Ab / dsDNA复合物激活的血小板通常含有数量减少的分泌性α颗粒，这些颗粒聚集在中间，并经常合并成一个固体电子密集区。许多活化的血小板释放出质膜来源的微泡和/或分解成亚细胞质碎片。共聚焦显微镜显示，与对照血小板中的均匀分布相比，抗dsDNA Ab / dsDNA复合物处理的血小板具有septin2的异质分布。结构性扰动伴随着线粒体去极化和血小板ATP含量降低，表明精力充沛。用抗FcγRIIA的单克隆mAb预处理可预防抗dsDNA Abs和抗dsDNA Ab / dsDNA复合物诱导的血小板中大多数生化和形态变化。数据汇总表明，单独的抗dsDNA抗体或与dsDNA复合的抗dsDNA抗体通过FcγRIIA受体强烈影响血小板。抗核抗体对血小板的免疫激活可能包括一种血栓形成机制，可能是SLE患者血栓并发症高风险的基础。