Association of circulating Treg and plasma microRNA-21 with rheumatoid arthritis progression.

Abstract

The etiology of rheumatoid arthritis (RA) is multifaceted. One of the hypothesized pathways that results in the progression of RA is regulatory T cell (Treg) dysfunction. The pro-osteoclastogenic and immunogenic characteristics of microribonucleic acid (microRNA)-21 (miR-21) suggest its role in RA progression. Hence, we investigated the significance of plasma miR-21 and Treg cell frequency as biomarkers for RA progression and assessed the link between miR-21 and Treg frequency in RA. This study enrolled 60 RA patients classified according to disease activity score 28-joint count with erythrocyte sediment rate (DAS28-ESR) to inactive cases (n = 30) and active cases (n = 30). Flow cytometer was used to assess Treg frequency. The Real-time quantitative PCR was used to measure the expression levels of miR-21 in plasma. When compared to the inactive group, the active group revealed significant up-regulation of miR-21 expression (p = 0.004) and down-regulation of Treg frequency (p < 0.001). While Treg frequency was negatively correlated, miR-21 fold change was positively correlated with DAS-28-ESR (r = -508, p < 0.001 and r = 0.334, p < 0.009, respectively). No correlation was detected between mirR-21 and Treg frequency. Treg distinguished the two groups at area under the curve (AUC) of 0.907 with 86.7% sensitivity and 73.3% specificity, whereas miR-21 up-regulation discriminated active from inactive RA patients at AUC of 0.717, with 83.3% sensitivity and 53.3% specificity. In conclusion, Treg frequency and miR-21 fold were differentially linked to DAS-28-ESR in RA. MiR-21 fold up-regulation changes and Treg frequency down-regulation can be suggested as biomarkers for RA activity.