MIR-146A and TLR4 gene expression in predicting rheumatoid arthritis disease

Abstract

Disease Activity Score 28 (DAS28) isthe most widely used method for rheumatoid arthritis(RA) disease activity evaluation. However, it may not reflect disease activity accurately being a subjective tool dependent on patient's self-health assessment and evaluation of swollen and tender joint counts. Therefore, finding a suitable blood genetic marker for accurate monitoring of RA disease activity has become essential. Therefore, the aim of this study was to assess miR- 146a and TLR4 expression in PBMCs of RA patients and to study their value as potential molecular biomarkers for RA disease activity in comparison to DAS28 score. This study was conducted on 51 RA patients and 15 age and sex matched healthy subjects as control group. The relative gene expression levels of miR-146a and TLR4 were determined by reverse transcriptase quantitative real time polymerase chain reaction. There were statistically significant differences between patients and healthy controls as regards miR-146a and TLR4 expression. In addition, statistically significant differences were observed between different patients’ subgroups as regards miR-146a and TLR4 expression. Moreover, miR-146a and TLR4 expression levels showed significant positive correlationswith those of morning stiffness durations, tender joints counts, swollen joints counts, visual analogue scale values, erythrocyte sedimentation rates, CRP, Anti- CCP antibody and DAS28.MiR-146aillustrated the best performance characteristics particularly in differentiating between high and moderate disease activity grades, showing highest sensitivity and specificity.Furthermore, there was a statistically significant increase in the expression levels of miR-146a and TLR4 in PBMCs of RA patients with ankles and/or feet joints involvement, as compared with those without involvement.Conclusion: MiR-146a and TLR4 were overexpressed in PBMCs of RA patients and were correlated with disease activity and radiographic progression especially miR-146a.

Keywords: DAS28, Larsen score, RA, reverse transcriptase quantitative real time PCR.