Background and Objectives Identification of biomarkers for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. MiRNAs have features of potential biomarkers and an altered expression of miRNAs was shown in established RA. Our aim was to analyse RA-associated miR-223 and miR-16 in sera from patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome.
Materials and Methods Clinical characteristics were obtained in 34 patients with ERA at baseline and after 3 (M3) and 12 (M12) months therapy with DMARDs. Total RNA was isolated using phenol-chloroform extraction from whole sera obtained at baseline and M3. Peripheral blood mononuclear cells (PBMC) from healthy donors were treated with methotrexate (MTX, 25 ug/ml) in vitro. Expression of miR-223 and miR-16 was analysed by TaqMan Real-time PCR.
Results Levels of miR-223 significantly decreased following therapy (p = 0.002). In treatment naïve patients with ERA, the expression of miR-223 positively correlated with baseline DAS28 (p = 0.031), change in DAS28 (∆DAS28) from baseline to M3 (p = 0.014), baseline CRP (p = 0.008) and count of peripheral leukocytes (p = 0.007). The change in expression of miR-223 in sera may be attributable to the change in the count of leukocytes between baseline and M3 concluded from the positive correlations between these variables (p = 0.025). In addition, the expression of miR-223 in PBMC was down regulated by 15% (p = 0.001) after treatment with MTX.
Levels of miR-16 significantly increased (p = 0.008) after 3 months of therapy and the increase in miR-16 was associated with the decrease in DAS28 from M3 to M12 (p = 0.002).
Conclusions Our data support the potential of miR-223 to serve as a marker of disease activity in patients with treatment naïve ERA. Moreover, monitoring levels of miR-16 and miR-223 may become a useful tool to predict the disease outcome in patients with ERA.
Acknowledgement This work was supported by IMI BTCure, IAR, Masterswitch-PF7, Articulum, OPPA and MH CR project No. 023728.