Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Spain.
Unidad de Gestión Clínica Reumatología, Hospital Universitario Reina Sofía, Córdoba, Spain.
Haematologica. 2018 May;103(5):908-918. doi: 10.3324/haematol.2017.184416. Epub 2018 Mar 15.
We aimed to identify the plasma miRNA profile of antiphospholipid syndrome (APS) patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease biomarkers. Ninety APS patients and 42 healthy donors were recruited. Profiling of miRNAs by PCR-array in plasma of APS patients identified a set of miRNAs differentially expressed and collectively involved in clinical features. Logistic regression and ROC analysis identified a signature of 10 miRNA ratios as biomarkers of disease. In addition, miRNA signature was related to fetal loss, atherosclerosis, and type of thrombosis, and correlated with parameters linked to inflammation, thrombosis, and autoimmunity. Hard clustering analysis differentiated 3 clusters representing different thrombotic risk profile groups. Significant differences between groups for several miRNA ratios were found. Moreover, miRNA signature remained stable over time, demonstrated by their analysis three months after the first sample collection. Parallel analysis in two additional cohorts of patients, including thrombosis without autoimmune disease, and systemic lupus erythematosus without antiphospholipid antibodies, each displayed specific miRNA profiles that were distinct from those of APS patients. , antiphospholipid antibodies of IgG isotype promoted deregulation in selected miRNAs and their potential atherothrombotic protein targets in monocytes and endothelial cells. Taken together, differentially expressed circulating miRNAs in APS patients, modulated at least partially by antiphospholipid antibodies of IgG isotype, might have the potential to serve as novel biomarkers of disease features and to typify patients' atherothrombotic status, thus constituting a useful tool in the management of the disease.
我们旨在确定抗磷脂综合征 (APS) 患者的血浆 miRNA 谱,并研究特定循环 miRNA 作为非侵入性疾病生物标志物的潜在作用。招募了 90 名 APS 患者和 42 名健康供体。通过对 APS 患者血浆中的 miRNA 进行 PCR-array 分析,确定了一组差异表达并共同参与临床特征的 miRNA。逻辑回归和 ROC 分析确定了一组 10 个 miRNA 比值作为疾病生物标志物。此外,miRNA 特征与胎儿丢失、动脉粥样硬化和血栓形成类型有关,并且与与炎症、血栓形成和自身免疫相关的参数相关。硬聚类分析将代表不同血栓形成风险特征组的 3 个簇区分开来。在几个 miRNA 比值之间发现了组间的显著差异。此外,通过在第一次样本采集后三个月对其进行分析,miRNA 特征保持稳定。在另外两个患者队列(包括无自身免疫性疾病的血栓形成和无抗磷脂抗体的系统性红斑狼疮)中的平行分析显示,每个队列都显示出与 APS 患者不同的特定 miRNA 谱。此外,我们发现 IgG 型抗磷脂抗体促进了选定 miRNA 的失调及其在单核细胞和内皮细胞中的潜在动脉血栓形成蛋白靶标。总之,APS 患者中差异表达的循环 miRNA,至少部分由 IgG 型抗磷脂抗体调节,可能具有作为疾病特征的新型生物标志物的潜力,并将患者的动脉血栓形成状态定型,从而成为疾病管理的有用工具。