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. In vitro,
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.