Soluble CD40 Levels in Rheumatoid Arthritis: Association with Serum Cytokines and Autoantibody Status

Background: In rheumatoid arthritis (RA), the CD40-CD40L axis plays a key role in immune cell activation and the production of inflammatory mediators. Although the soluble form of CD40 (sCD40) has been identified and investigated in various autoimmune disorders, its significance in RA and its relationship with inflammatory and humoral markers remain to be fully elucidated. Methods: Sixty-two patients with RA, classified according to the 2010 ACR/EULAR criteria, and 31 age- and sex-matched healthy controls were included. Clinical characteristics, disease activity (DAS28-ESR), and acute-phase reactant levels (CRP and ESR) were evaluated in patients with RA. Autoantibodies (RF, ACPA, anti-MCV, and anti-PAD4), serum cytokines, and sCD40 levels were quantified using ELISA and multiplex bead-based assays. Group differences and associations were assessed using nonparametric tests. Multiple linear regression analysis was performed to account for potential confounding variables. Results: Serum sCD40 levels did not differ significantly between patients with RA and healthy controls or among patient subgroups stratified by disease activity or sex. No associations were observed between sCD40 levels and autoantibody seropositivity or titers. sCD40 levels were positively correlated with age (rs = 0.293, p = 0.02). Notably, after adjustment for age, sCD40 showed a significant negative correlation with IL-2 (rs = −0.317, p = 0.01). Conclusions: Serum sCD40 does not reflect disease activity or the humoral immune response in RA. Nevertheless, further studies are needed to evaluate its relevance during early stages of the disease and to further characterize its role in cytokine production.