The relationship of blood CDC42 level with Th1 cells, Th17 cells, inflammation markers, disease risk/activity, and treatment efficacy of rheumatoid arthritis

Abstract

Background Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. Methods After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. Results Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. Conclusion CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

Cell division control 42 elevates during infliximab therapy, and its increment relates to treatment response in ulcerative colitis patients

“…16,17 Furthermore, CDC42 is inversely correlated with disease activity score in 28 joints (DAS28), Bath ankylosing spondylitis disease activity index (BASDAI), and pediatric CD activity index (PCDAI) in RA patients, AS patients, and pediatric CD patients, respectively. [16][17][18] In the current study, CDC42 was negatively related to CRP, TNFα, IL-1β, IL-17A, and Mayo score in active UC patients, which could be explained as that: (a) CDC42 mediated multiple signaling pathways to suppress the inflammatory markers and cytokines in UC patients. 24,25 (b) CDC42 was related to less intestinal inflammation as mentioned earlier, which prevented the intestinal mucosal barrier from irritation and disruption, therefore leading to lower disease activity of UC patients.…”

“…For instance, CDC42 is reduced in AS patients, RA patients, and pediatric CD patients compared with controls. [16][17][18] Also, CDC42 is related to a lower risk of active CD in children, 18 while the clinical value of CDC42 in UC patients remains exclusive.…”

“…For instance, CDC42 is negatively related to CRP in both RA patients and AS patients. 16,17 Furthermore, CDC42 is inversely correlated with disease activity score in 28 joints (DAS28), Bath ankylosing spondylitis disease activity index (BASDAI), and pediatric CD activity index (PCDAI) in RA patients, AS patients, and pediatric CD patients, respectively. [16][17][18] In the current study, CDC42 was negatively related to CRP, TNFα, IL-1β, IL-17A, and Mayo score in active UC patients, which could be explained as that: (a) CDC42 mediated multiple signaling pathways to suppress the inflammatory markers and cytokines in UC patients.…”

“…15 In the clinical field, CDC42 has shown both diagnostic and prognostic values for multiple autoimmune diseases (including rheumatoid arthritis (RA), ankylosing spondylitis (AS), and pediatric Crohn's disease (CD)), while its clinical role in UC patients remains indistinct. [16][17][18] Hence, this study aimed to detect CDC42 longitudinal change during IFX treatment and its association with IFX response in UC patients.…”

DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology

“…Th1 and Th17 cell subsets contribute to inflammation in RA. Many studies have shown that the inhibition of Th1 and Th17 cell subsets can alleviate RA (77)(78)(79). Th2 cell subsets can inhibit Th1 and Th17 cell differentiation and function by secreting IL-4 as a mechanism to antagonize inflammation (80).…”