MicroRNA-146a expression as a potential biomarker for rheumatoid arthritis in Egypt

Abstract

Background: MicroRNAs (miRNAs) are small non-coding RNAs, whose role in regulating diverse immune functions, suggests they might play a role as biomarkers for immune mediated disorders. Studies showed that miRNA-146a (miR-146a) expression is increased by proinflammatory cytokines and is an important modulator of differentiation and function of cells of innate and adaptive immunity.
Aim of the work: The current study aimed to evaluate the expression of miR-146a as a potential biomarker for diagnosis of rheumatoid arthritis (RA) and to explore its association with disease activity.
Subjects and methods: The study enrolled 50 Egyptian subjects divided into a patient group, which comprised 25 RA patients, and a control group which comprised 25 healthy individuals. The disease activity for the patients’ group was determined by simplified disease activity index. Relative quantification of miR-146a expression in whole blood was determined using reverse transcriptase quantitative real time polymerase chain reaction.
Results: There were highly significant statistical differences between patients and healthy controls as regards miR-146a relative expression, erythrocyte sedimentation rate (ESR) and anticyclic citrullinated peptide (anti-CCP) (p< 0.001). Highly significant statistical differences (p< 0.001) were also found between different patients’ subgroups as regards miR-146a relative expression and ESR. miR-146a levels correlated positively with those of ESR, C-reactive protein and anti-CCP (p< 0.001). miR-146a illustrated best performance in diagnosing RA, showing the highest sensitivity and specificity (96% and 100%, respectively) (AUC: 0.992 at a cut off value of P2.16) compared to anti-CCP (sensitivity: 68%, specificity: 100% and AUC: 0.87 at a cut off value of P22 U/ml) and RF (sensitivity: 56%, specificity: 80% and AUC: 0.992 at a cut off value of P13 U/ml).
Conclusion: This study demonstrated that miR-146a expression was highly significantly elevated in whole blood of patients with RA. Its diagnostic performance was better than anti-CCP and RF and its level of expression correlates with disease activity.