Efficacy of DMARDs Therapy on the Disease Activity and Gene Expression Levels of FoxO1, FoxO3, Runx1, and Runx3 in Early Rheumatoid Arthritis Patients: A Pre-Post Interventional Study With Healthy Controls.

Background and Aims: Forkhead box O (FoxO) transcription factors exert crucial roles in immune responses. Besides, the Runt-related transcription factor (Runx) family plays a pivotal role in the development and homeostasis of cartilage and bone. This study assessed the plasma concentrations of the pro-inflammatory interleukin-6 (IL-6) cytokine and the anti-inflammatory cytokine interleukin-10 (IL-10), as well as the gene expression levels of FoxO1, FoxO3, Runx1, and Runx3, in the peripheral blood sample of the early rheumatoid arthritis (RA) patients treated with conventional disease-modifying antirheumatic drugs (DMARDs) for 6 months relative to normal subjects. Methods: This study examined 30 early DMARDs-naïve RA patients (before and after treatment) and 30 age- and gender-matched normal individuals. The plasma levels of IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression amounts of FoxO1, FoxO3, Runx1, and Runx3 were determined using real-time PCR. Results: The plasma IL-6 concentrations increased significantly in pre- and posttreatment RA patients compared with controls (p < 0.001). Moreover, the gene expression of FoxO1 and FoxO3 was enhanced considerably in RA patients (both before and after treatment), compared to controls (p < 0.001 for FoxO1 and p = 0.02 and p = 0.01 for FoxO3, respectively). Runx1 gene expression increased dramatically in pre- and posttreatment RA patients compared with the controls (p < 0.001). Runx3 gene expression was meaningfully enhanced in pretreatment RA patients than in normal controls (p < 0.001). Also, DMARDs treatment strikingly reduced Runx3 gene expression levels compared to pretreatment levels (p < 0.001). Conclusion: DMARDs treatment dramatically diminishes Runx3 gene expression, thereby lowering disease activity and inflammatory markers in the early RA patients.