JNK Pathway-Associated Phosphatase as a Serum Marker for Disease Activity and Treatment Outcome of Juvenile Idiopathic Arthritis

Background JNK pathway‐associated phosphatase (JKAP) involves in the regulation of inflammation, immunity, and lung injury. The current study aimed to investigate correlation of JKAP with Th1, Th17 cells, acute exacerbation risk, and disease severity in chronic obstructive pulmonary disease (COPD) patients. Methods Totally, 45 stable COPD (SCOPD) patients, 45 acute exacerbation COPD (AECOPD) patients, and 45 controls were enrolled. Serum was collected for JKAP, interferon‐gamma (IFN‐γ) (Th1 cytokine), and interleukin 17 (IL‐17) (Th17 cytokine) detection. Besides, peripheral blood mononuclear cell from COPD patients was collected for evaluating Th1 and Th17 cells. Results JKAP was highest in controls followed by SCOPD patients and lowest in AECOPD patients (median: 105.673 vs. 75.374 vs. 41.807 pg/ml, p < 0.001). Meanwhile, receiver operating characteristic (ROC) curves revealed that JKAP differentiated the AECOPD patients from the controls (area under curve (AUC): 0.910 (95% confidence interval (CI): 0.849–0.970)) and AECOPD patients from SCOPD patients (AUC: 0.726 (95% CI: 0.622–0.830)). Moreover, JKAP positively correlated with FEV1 (%predicted) in AECOPD patients (r = 0.347 p = 0.019). Additionally, JKAP was negatively correlated with the GOLD stage in AECOPD patients (r = −0.344, p = 0.021) and SCOPD patients (r = −0.357, p = 0.016). Whereas, JKAP was not associated with other clinical features (all p > 0.05). Besides, JKAP was negatively linked with Th17 cells (r = −0.378, p = 0.010), IFN‐γ (r = −0.358, p = 0.016), IL‐17 (r = −0.414, p = 0.005) in AECOPD patients and Th17 cells (r = −0.342, p = 0.022), IL‐17 (r = −0.299, p = 0.046) in SCOPD patients. Conclusion Downregulated JKAP correlates with Th17 cells, higher acute exacerbation risk, and severity in COPD patients, indicating its underlying potency as a biomarker for COPD.

Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 40%

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Circulating JNK pathway‐associated phosphatase: A novel biomarker correlates with Th17 cells, acute exacerbation risk, and severity in chronic obstructive pulmonary disease patients

Gao

Feng

et al. 2021

“…Since DUSP22 is a regulator of T‐cell activation and differentiation, the correlation of blood DUSP22 dysregulation with inflammation is identified in several diseases featured by dysregulated immune or inflammation. 12 , 20 , 21 , 24 , 25 , 26 , 27 For instance, serum DUSP22 relates to decreased CRP, number of joints with active arthritis, physician's global assessment of disease activity in juvenile idiopathic arthritis patients. 25 In addition, serum DUSP22 correlates with less sever inflammation and disease activity in Crohn disease patients.…”

Section: Discussionmentioning

confidence: 99%

“… 12 , 20 , 21 , 24 , 25 , 26 , 27 For instance, serum DUSP22 relates to decreased CRP, number of joints with active arthritis, physician's global assessment of disease activity in juvenile idiopathic arthritis patients. 25 In addition, serum DUSP22 correlates with less sever inflammation and disease activity in Crohn disease patients. 27 Furthermore, a previous study also observes that serum DUSP22 level reflects decreased ESR, CRP, and DAS28 score in RA patients 14 ; then, another study also reports its hypomethylation relates to disease activity of RA.…”

Section: Discussionmentioning

confidence: 99%

Measurement of synovium and serum dual specificity phosphatase 22 level: Their inter‐correlation and potency as biomarkers in rheumatoid arthritis

Chen

et al. 2021

Background Dual specificity phosphatase 22 (DUSP22), also named as Jun N‐terminal kinase pathway associated phosphatase recently, is reported to be closely engaged in immune and inflammation regulation. This study aimed to investigate the interaction between synovium DUSP22 and serum DUSP22 levels and to explore their correlation with rheumatoid arthritis (RA) risk, inflammation, and disease activity. Methods Synovium and serum samples from 42 RA patients with knee involvement underwent arthroscopy, and 20 knee trauma patients were collected. Besides, serum samples from 40 healthy controls were also obtained. Synovium DUSP22 expression was detected by reverse transcription quantitative polymerase chain reaction, while serum DUSP22 level was detected by enzyme‐linked immunosorbent assay. Results Synovium DUSP22 level was greatly decreased in RA patients compared to trauma controls (p < 0.001), and it was negatively correlated with tender joint count (TJC) (r = −0.318, p = 0.040), C‐reactive protein (CRP) (r = −0.330, p = 0.033), and Lysholm score (r = −0.423, p = 0.005) in RA patients. Serum DUSP22 level was lowest in RA patients, followed by trauma controls, then highest in healthy controls (p < 0.001). Serum DUSP22 level was negatively associated with TJC (r = −0.438, p = 0.004), swollen joint count (SJC) (r = −0.372, p = 0.015), CRP (r = −0.391, p = 0.011), and disease activity score in 28 joints (DAS28ESR) score (r = −0.406, p = 0.008), and it increased after treatment (p = 0.001) in RA patients. In addition, serum DUSP22 level positively related to synovium DUSP22 level in RA patients (r = 0.394, p = 0.010). Conclusion Synovium and serum DUSP22 are intercorrelated and insufficiently expressed in RA patients; meanwhile, their deficiency correlates with increased systemic inflammation, disease activity, and joint dysfunction.

Dual specificity phosphatase 22 relates to skin lesion degree and biologics history, while its longitudinal elevation during treatment reflects better outcome in psoriasis patients

Cailing

Fang

et al. 2021

Background Dual specificity phosphatase 22 (DUSP22) plays an important role in the regulation of immune and inflammation, but its correlation with clinical features and treatment outcome in psoriasis patients is still unclear. This study was to investigate the longitudinal change of DUSP22 with time, as well as its association with disease activity and treatment response in psoriasis patients. Methods Totally, 120 psoriasis patients, 50 patients with other skin inflammations as disease controls (DCs), and 50 health controls (HCs) were recruited. Serum samples were collected from psoriasis patients at baseline, month (M)1, M3, and M6 after initiation of etanercept‐based treatment as well as from DCs and HCs after enrollment to assess DUSP22 level by enzyme‐linked immunosorbent assay. Results DUSP22 was lower in psoriasis patients than in HCs and DCs (both p < 0.001). Besides, in psoriasis patients, DUSP22 was associated with lower psoriasis area severity index (PASI) score (p = 0.001) and systemic biological treatment history (p = 0.023), but not with other demographics, disease characteristics, or treatment history (all p>0.05). In addition, DUSP22 was increased with time (p < 0.001) in total patients. Moreover, DUSP22 at M3 (p = 0.004) and M6 (p < 0.001) was higher in response patients than in non‐response patients evaluated by PASI 75. Additionally, DUSP22 at M3 (p < 0.001) and M6 (p = 0.003) was also increased in response patients compared with non‐response patients evaluated by PASI 90. Conclusion DUSP22 decreases and negatively correlates with disease activity, while its longitudinal elevation with time reflects satisfactory treatment response in psoriasis patients.