Abstract
Background: MicroRNAs (miRNAs) are a class of small, non-coding RNAs that negatively regulate gene expression at posttranscriptional level. In the recent years studies have shown that in rheumatoid arthritis (RA) the systemic and local expression of certain miRNAs is altered [1-2]. The correlation between their expression levels and scores for disease activity and progression in RA make them possible candidate for biomarkers in the clinical practice. Objectives: To analyze the expression levels of miR-146a and miR-223 in synovial fluid (SF) from RA patients in regard to the ultrasound scores for disease activity. Methods: A total number of 48 RA patients according to the 1987 ACR criteria were included in the study. Expression levels of miR-146a and miR-223 SF were determined by qPCR (SybrGreen technology) and compared to healthy controls (HCs). Relative changes of gene expression levels of the studied miRNAs were calculated by 2-ΔΔCt method. Musculoskeletal ultrasound (MSUS) examination was performed by two independent examiners on ESAOTE, MyLab60 using both grey scale and power Doppler technic. A semi quantitative assessment of the peripheral joints was performed for detecting joint inflammation and determining the grade of synovial thickening and the degree of vascularization. Ultrasound features for active disease were correlated to the local expression of the studies miRNAs. SPSS was used for statistical analysis. Results: RA SF showed overexpression of miR-146a (in 70.83%, p=0.007) and of miR-223 (in 79.17%, p=1.64x10-3) when compared to HCs. There was a statistically significant correlation between the presence of synovitis and the degree of the power Doppler signal on MSUS and the local expression of miR-146a (p=0.030 and p=0.049, respectively) and miR-223 (p=6.19 x 10-4 and p=0.003, respectively). SF levels of miR-223 correlated also with the degree of synovial hypertrophy on MSUS (p = 0.013). Conclusion: We found correlation between the SF expression of miR-146a and miR-223 and the ultrasound features of active joint inflammation. Further analysis with larger sets is needed to confirm if altered local miRNA expression could be used in the clinical practice as biomarker for disease activity especially in cases with subclinical synovitis.
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