Background/Purpose: Epigenetic anomalies are emerging as striking pathogenic features of autoimmune disorders. MicroRNAs (miRNAs) are small non-coding RNAs with a key role in regulatory networks that might represent a novel class of disease biomarkers. Yet, the contribution of circulating miRNAs to the pathogenesis of antiphospholipid syndrome (APS) and their potential role as biomarkers of this disease are still unknown. Purpose: To determine the circulating miRNA signature of APS and to identify potential circulating microRNAs that might represent non-invasive biomarkers of the disease.

Methods: Total RNAs were isolated from plasma of 10 APS patients and 10 healthy controls, cDNA transcribed and pooled, and human plasma miRNA polymerase chain reaction (PCR) arrays were performed. Then, selected miRNAs were analyzed in a validation cohort consisting of 72 APS patients and 38 healthy donors.  To evaluate their patho-physiological relevance, a functional analysis was conducted by using the Ingenuity Pathway Analysis (IPA) software. Association and correlation studies with clinical and serological variables were also performed.

Results: miRNA-PCR-Array showed that 22 circulating microRNAs were differentially expressed in APS patients in relation to the control group (fold change≥2). IPA analysis indicated that a high number of these microRNAs had targets mainly involved in processes related to cardiovascular disease (40%, including arteriosclerosis, hypertension, and coronary artery disease) inflammatory response (50%), and reproductive system disease (45%, i.e endometriosis and preeclampsia). Validation analysis by RT-PCR showed that the levels of three microRNAs (miR-19b, miR-20a and miR-296) were significantly increased in plasma of APS patients. These miRNAs have been further demonstrated to be specifically involved in preeclampsia (miR-296), inflammation and thrombosis (miR-19b and -20a) in other autoimmune and inflammatory disorders. Receiver operating characteristics (ROC) curve analysis showed that the ratio of combination for the three miRNAs could discriminate APS patients from healthy donors with a 70% of sensitivity and specificity and an area under curve (AUC) close to 1 (0,72), thus pointing at these microRNAs as potential diagnostic biomarkers of APS. Analysis of interrelation with clinical variables showed that the expression levels of miR-296 were associated with the occurrence of recurrent thrombosis, while the expression levels of miR-20a were most specifically linked to episodes of arterial thrombosis, and further correlated with the erythrocyte sedimentation rate.

Conclusion: We have identified a set of serum miRNAs as potential APS biomarkers, primarily involved in key clinical features of this autoimmune condition. 

Supported by CTS-7940, PI12/01511, SER.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-mirnas-as-potential-disease-biomarkers-in-antiphospholipid-syndrome-patients/