Treatment-associated changes in SESN2, NFATC1, and NRF2 gene expression in rheumatoid arthritis: a comparative study of newly diagnosed and DMARD-treated patients

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by uncontrolled joint inflammation and progressive structural damage in the joints. Sestrin 2 ( SESN2 ) and nuclear factor erythroid-related 2 ( NRF2 ) acts as critical regulators of cellular redox homeostasis and autophagy, while nuclear factor of activated T cells 1 ( NFATC1 ) acts as an early transcriptional stimulator of osteoclastogenesis. This study evaluated the transcriptional profiles of SESN2 , NRF2 , and NFATC1 in peripheral blood mononuclear cells (PBMCs) to evaluate their utility as potential biomarkers in untreated and DMARD-treated RA groups. SESN2 expression was significantly increased in newly diagnosed RA patients compared with DMARD-treated subjects ( p = 0.029) and controls ( p = 0.004). Similarly, NRF2 expression showed an upward trend in the untreated group compared with treated patients and controls, although these differences did not reach statistical significance ( p = 0.088 & p = 0.103). Conversely, NFATC1 transcription showed a subtle downward trend in both RA patients subgroups compared with the control group, without reaching statistical significance ( p = 0.176 & p = 0.095). These findings suggest that SESN2 expression is associated with the clinical/treatment status of RA and may warrant further investigation as a potential molecular marker. However, further studies with larger sample sizes are needed to clarify the potential roles of NRF2 and NFATC1 in RA pathogenesis and response to treatment.