JNK pathway-associated phosphatase illustrates low expression and negative correlations with inflammation, disease activity, and T-helper 17 cells in inflammatory bowel disease children

Abstract

Background: C-Jun N-terminal kinase pathway-associated phosphatase (JKAP) modulates the T cell receptor and mitogen-activated protein kinase pathway-mediated autoimmunity, thus participating in the pathogenesis of autoimmune diseases. This study aimed to explore the clinical implication of JKAP in inflammatory bowel disease (IBD) children.

Methods: C-Jun N-terminal kinase pathway-associated phosphatase, tumor necrosis factor-α (TNF-α), interleukin-23, interferon-γ (T-helper 1 secreted cytokine), and interleukin-17A (T-helper 17 secreted cytokine) in serum samples from 140 IBD children (including 60 Crohn's disease (CD) children and 80 ulcerative colitis (UC) children) were detected by ELISA. Meanwhile, JKAP from serum samples of 10 healthy controls (HCs) was also detected by ELISA.

Results: C-Jun N-terminal kinase pathway-associated phosphatase was reduced in CD children (median (interquartile range (IQR)): 51.6 (36.8-69.5) pg/ml) and UC children (median (IQR): 57.5 (43.4-78.5) pg/ml) compared with HCs (median (IQR): 101.8 (70.0-143.2) pg/ml) (both p < 0.05). In CD children, JKAP was negatively correlated with C-reactive protein (CRP) (p = 0.016) and erythrocyte sedimentation rate (ESR) (p = 0.029); while in UC children, JKAP was also negatively correlated with CRP (p = 0.006) and ESR (p = 0.022). Regarding the correlation of JKAP with disease activity, it presented negative correlations with PCDAI (p = 0.001) and PUCAI (p = 0.002). Besides, JKAP was negatively related to TNF-α (both p < 0.05) but not interleukin-23 (both p>0.05) in CD and UC children. Additionally, JKAP was not correlated with interferon-γ in CD or UC children (both p>0.05), while negatively correlated with interleukin-17A in CD and UC children (both p < 0.05).

Conclusion: C-Jun N-terminal kinase pathway-associated phosphatase shows low expression and negative correlations with inflammation, disease activity, and T-helper 17 cells in IBD children.

Keywords: C-Jun N-terminal kinase pathway-associated phosphatase; T-helper 17; disease activity; inflammation; inflammatory bowel disease children.

FIGURE 1

C‐Jun N‐terminal kinase pathway‐associated phosphatase expression in IBD children and HCs. Comparison of JKAP expression among UC children, CD children, and HCs (A); Ability of JKAP in discriminating UC and CD children from HCs (B)

FIGURE 2

Correlation of JKAP with inflammatory markers in IBD children. Correlation of JKAP with CRP (A) and ESR (B) in CD children; correlation of JKAP with CRP (C) and ESR (D) in UC children

FIGURE 3

Correlation of JKAP with disease activity in IBD children. Correlation of JKAP with PCDAI (A) and comparison of JKAP among patients with different severity (B) in CD children; correlation of JKAP with PUCAI (C) and comparison of JKAP among patients with different severity (D) in UC children

FIGURE 4

Correlation of JKAP with proinflammatory cytokines in IBD children. Correlation of JKAP with TNF‐α (A) and IL‐23 (B) in CD children; correlation of JKAP with TNF‐α (C) and IL‐23 (D) in UC children

FIGURE 5

Correlation of JKAP with cytokines secreted by Th1 and Th17 in IBD children. Correlation of JKAP with IFN‐γ (A), IL‐17A (B), and IFN‐γ/IL‐17A ratio (C) in CD children; correlation of JKAP with IFN‐γ (D), IL‐17A (E), and IFN‐γ/IL‐17A ratio (F) in UC children

FIGURE 6

Correlation of JKAP with treatment in IBD children. Comparison of JKAP in CD children with or without 5‐ASA (A), glucocorticoid (B), immunosuppressant (C), or biologics (D) treatment. Comparison of JKAP in UC children with or without 5‐ASA (E), glucocorticoid (F), immunosuppressant (G), or biologics (H) treatment