PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

Abstract

Objective Cell division cycle 42 (CDC42) regulates the polarization of M2 macrophage and maintains the T cell homeostasis, to participate in multiple autoimmune diseases, while its clinical involvement in ankylosing spondylitis (AS) remains unclear. Hence, the current study aimed to investigate the correlation of CDC42 with clinical characteristics and treatment outcome in AS patients receiving tumor necrosis factor (TNF) inhibitor therapy. Methods Peripheral blood mononuclear cell (PBMC) CDC42 expression was detected at baseline, week (W) 4, W8, and W12 after TNF inhibitor treatment in 91 AS patients and in 50 HCs after enrollment. Furthermore, serum TNF‐α, interferon‐γ (IFN‐γ), interleukin‐10 (IL‐10), and interleukin‐17A (IL‐17A) from AS patients were detected at baseline. Results Blood CDC42 was lower in AS patients compared with HCs (p < 0.001). Additionally, blood CDC42 was negatively linked with CRP (r = −0.349, p = 0.001), BASDAI score (r = −0.243, p = 0.020), and ASDASCRP score (r = −0.238, p = 0.023) in AS patients; however, blood CDC42 was not correlated with other clinical characteristics. Besides, CDC42 was negatively correlated with TNF‐α (r = −0.237, p = 0.024) and IL‐17A (r = −0.339, p = 0.001) but not with IFN‐γ (p = 0.083) or IL‐10 (p = 0.280). Moreover, blood CDC42 was elevated after TNF inhibitor treatment (p < 0.001). Meanwhile, blood CDC42 was not varied at baseline and W4 between response patients and non‐response patients, while it was higher at W8 (p = 0.019) and W12 (p = 0.002) in response patients than in non‐response patients after treatment. Conclusion Blood CDC42 deficiency links with elevated pro‐inflammatory cytokines, disease activity and unsatisfying response to TNF inhibitor in AS patients.

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

“…CDC42 is previously reported to be associated with etanercept response in AS patients, while the correlation of CDC42 with IFX response in UC patients has not been determined. 17 Then, CDC42 at W0 and W12 was detected in the current study aiming to observe its longitudinal change during IFX treatment, and it was observed that CDC42 was elevated during IFX treatment in active 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.…”

“…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.…”

“…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.…”