Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder characterized by thromboembolic episodes and pregnant morbidity with an increasing clinical importance. To gain insight into the pathogenesis of PAPS, we have investigated the gene expression profiles that characterize peripheral blood mononuclear cells derived from PAPS patients. We show that the transcriptional activity of genes involved in innate immune responses, such as toll-like receptor 8 and CD14, as well as downstream genes of this pathway, such as STAT1, OAS2, TNFSF13 and PLSCR1 are significantly increased in PAPS patients. In addition, the expression of monocyte-specific cytokines is also elevated in PAPS mononuclear cells stimulated in vitro with lipopolysaccharide. Taken together, these results reveal a 'response to pathogen' signature in PAPS, which could reflect an altered monocyte activity. Finally, microarray analyses also revealed a reduced expression of genes coding for proteins involved in transcriptional control. Interestingly, a significant proportion of them exhibit E2F-binding sites in their promoter, suggesting that a deregulated RB/E2F activity could play a role in the pathogenesis of antiphospholipid syndrome.

中文翻译：

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先天性免疫反应基因表达谱表征原发性抗磷脂综合征。

原发性抗磷脂综合征（PAPS）是一种全身性自身免疫性疾病，其特征是血栓栓塞发作和孕妇发病，其临床重要性日益增加。为了深入了解PAPS的发病机理，我们研究了表征PAPS患者外周血单个核细胞特征的基因表达谱。我们显示，在PAPS患者中，涉及先天免疫应答的基因（例如通行费样受体8和CD14）以及该途径的下游基因（例如STAT1，OAS2，TNFSF13和PLSCR1）的转录活性显着增加。另外，在体外用脂多糖刺激的PAPS单核细胞中单核细胞特异性细胞因子的表达也升高。总而言之，这些结果揭示了PAPS中“对病原体的反应”特征，这可能反映了单核细胞活性的改变。最后，微阵列分析还揭示了编码参与转录控制的蛋白质的基因的表达减少。有趣的是，它们中的很大一部分在其启动子中显示E2F结合位点，表明RB / E2F活性的失调可能在抗磷脂综合征的发病机理中起作用。