Associations of circulating cell-free microRNA with vasculopathy and vascular events in systemic lupus erythematosus patients

S. Kay*, A. Carlsen, A. Voss, M. Burton, ACP Diederichsen, M. K. Poulsen, NHH Heegaard

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a high risk of atherosclerosis and cardiovascular disease (CVD). MicroRNAs (miRNAs) are small non-coding RNAs that modulate protein translation, and dysregulation is seen in autoimmunity, atherosclerosis, and CVD. We investigate associations between circulating miRNAs and markers of atherosclerosis in SLE patients. Method: A group (n = 121) of well-characterized SLE patients were screened for atherosclerosis by cardiac computed tomography and carotid ultrasound. RNA was purified from plasma and 46 specific miRNAs were determined using quantitative real-time polymerase chain reaction. Results: Forty-one miRNAs were consistently detected. Fifty out of 118 available SLE patients had atherosclerosis. A profile consisting of three miRNAs (decreased miR-125b, miR-101, miR-375) was indicative of atherosclerosis. Multivariate logistic regression identified eight clinical manifestations associated with atherosclerotic outcome. The full classification profile showed a specificity of 88% and a sensitivity of 86%. Hierarchical clustering identified an eight-miRNA profile that differentiated a subgroup of SLE patients (n = 16) who had significantly increased venous thrombotic events (p = 0.045), a higher prevalence of β2-glycoprotein I antibodies (p = 0.029), and an increased prevalence of thrombocytopenia (p = 0.028). Conclusion: In this cross-sectional study, the circulating miRNA profile distinguished SLE patients with atherosclerosis from those without. Furthermore, an eight-miRNA signature was associated with thrombocytopenia, venous thrombotic events, and β2-glycoprotein I antibodies in SLE patients. Prospective studies are needed to confirm the findings and to establish the precise role of circulating miRNA profiling in the evaluation of atherosclerosis in SLE.

Original languageEnglish
JournalScandinavian Journal of Rheumatology
Volume48
Issue number1
Pages (from-to)32-41
ISSN0300-9742
DOIs
Publication statusPublished - Jan 2019

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