Serum CDC42 is increased during tumor necrosis factor inhibitor treatment, and its elevation correlates with satisfactory treatment response in rheumatoid arthritis patients.

Abstract

Our previous study discovered that cell division control protein 42 (CDC42) correlated with decreased disease activity and risk of developing rheumatoid arthritis (RA), along with repressed T helper type 17 cell differentiation. This study aimed to further estimate the longitudinal change of serum CDC42 and its association with treatment outcomes to tumor necrosis factor inhibitor (TNFi) in RA. CDC42 was detected in serum by ELISA at week (W)0, W6, W12, and W24 in 88 RA patients undergoing TNFi treatment, and after enrollment in 20 disease controls (DCs) and 20 healthy controls (HCs). CDC42 was lower in RA patients compared with DCs and HCs (both p < .001); meanwhile, it negatively related to C-reactive protein (p = .011) and DAS28 score (p = .006). Regarding TNFi type, 40.9%, 33.0%, 17.0%, and 9.1% of patients received adalimumab, etanercept, golimumab, and infliximab, respectively. Notably, CDC42 was increased from W0 to W24 in RA patients receiving TNFi treatment (p < .001), also in patients receiving adalimumab (p < .001), etanercept (p < .001), golimumab (p < .001), and infliximab (p = .001). Furthermore, CDC42 at W24 was higher in patients with a clinical response to TNFi treatment compared with those without (p = .023); CDC42 at W12 (p = .027) and W24 (p = .002) was elevated in patients with clinical low disease activity in response to TNFi treatment versus those without; whereas CDC42 at W12 (p = .074) and W24 (p = .068) only showed an increasing trend in patients with clinical remission with TNFi treatment, but did not achieve statistical significance. Circulating CDC42 is elevated during TNFi administration; its increase reflects good 24-week TNFi treatment responses in RA patients.