JNK pathway‐associated phosphatase associates with rheumatoid arthritis risk, disease activity, and its longitudinal elevation relates to etanercept treatment response

Lee, Sun; Tu, Jianxin; Chen, Xiaowei; Dai, Meijie; Xia, Xiaoru; Liu, Cailong; Zhou, Yan

doi:10.1002/jcla.23709

Cited by 9 publications

(21 citation statements)

References 27 publications

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“…JKAP, as one key member of DUSP family, is reported to possess clinical value reflecting disease risk and severity of several immune/inflammatory‐related disease and neurological diseases. For instance, a study uncovers that serum JKAP is downregulated in rheumatoid arthritis patients compared to controls, and it is negatively correlated erythrocyte sedimentation rate, C‐reactive protein and disease activity in RA patients 6 ; another study discloses that blood JKAP reduction correlates with asthmatic exacerbation and pro‐inflammatory cytokines in asthmatic children 7 ; furthermore, some reports discovers that JKAP hypermethylation exists and correlates with TAU phosphorylation in AD patients, as well as is involved in the interaction between utero famine exposure and schizophrenia 9,10 …”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we performed the current study and observed that serum JKAP was greatly decreased in PD patients compared to controls, correlates with lower UPDRS‐I score, UPDRS‐II score while higher MMSE score in PD patients. The possible explanations include: (1) JKAP insufficiency decreased neuro viability and function via its hypermethylation and inflammation regulation; therefore, it was downregulated in PD patients compared to controls, and correlated with some part of UPDRS scores 6–10 ; (2) JKAP inactivated T‐cell signaling and interacted with Th1 as well as Th17, resulting in aberrant immune environment and inflammation to affect PD progression; therefore, it correlated with some part of UPDRS scores and MMSE score 8,11–13,20,21 ; (3) JKAP repressed Th17 cell differentiation, the latter was closely involved in the cognitive impairment in neurological diseases including PD; therefore, JKAP correlated with MMSE score 22 …”

Section: Discussionmentioning

confidence: 99%

“…JNK pathway‐associated phosphatase (JKAP), also named as dual specificity protein phosphatase 22 (DUSP22), is reported to be involved in the regulation of immunity and inflammation; meanwhile, it is also implicated in the development and progression of neurological diseases 6–10 . For instance: JKAP inhibits T‐cell receptor signaling and autoimmunity via regulating Lck and MAP4K family kinases 8,11 ; meanwhile, it represses CD4 + T‐cell differentiation into Th1 and Th17 cells in systemic lupus erythematosus nephritis and inflammatory bowel disease 12,13 ; Furthermore, it modifies PKA‐dependent phosphorylated TAU and CREB activation in Alzheimer disease, and is aberrant in schizophrenia 9,10 .…”

Section: Introductionmentioning

confidence: 99%

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JKAP relates to disease risk, severity, and Th1 and Th17 differentiation in Parkinson's disease

Yang

Zhuang

Cai

et al. 2021

Ann Clin Transl Neurol

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Objective JNK pathway‐associated phosphatase (JKAP) is previously reported to regulate immune/inflammatory process via T‐cell signaling, and closely involves in neurological diseases, while its implication in Parkinson's disease (PD) is unknown. Therefore, this study aimed to investigate the correlation of JKAP with Th1/Th2/Th17 cells and their clinical roles in PD patients, and then further explore the effect of JKAP on regulating CD4+ T‐cell differentiation in PD. Methods Totally 50 PD patients and 50 age‐/gender‐matched controls were enrolled. Their blood samples were collected and proposed to ELISA and flow cytometry assays for JKAP, Th1, Th2, and Th17 measurements. In vitro, CD4+ T cells were isolated from PD patients then transfected with JKAP overexpression and knockdown Lentivirus, followed by detection of markers (CD25+ cell proportion, CD69+ cell proportion, IFN‐γ, IL10, and IL17). Results JKAP was downregulated in PD patients compared to controls, which also showed good potency to discriminate them. Besides, JKAP negatively correlated with Th1 and Th17 cell proportions, but did not associate with Th2 cell proportion in PD patients; Interestingly, JKAP did not correlated with Th1, Th2, or Th17 cell proportions in controls. Furthermore, JKAP correlated with some parts of unified Parkinson’s Disease Rating Scale (UPDRS) and Mini‐Mental State Examination (MMSE) score. In vitro, JKAP overexpression repressed CD4+ T‐cell activation and its differentiation into Th1 and Th17 cells in PD, while JKAP knockdown appeared opposite effect. Interpretation JKAP associates with disease risk and severity, correlates with Th1 and Th17 cells, and regulates CD4+ T‐cell activation/differentiation in PD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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JKAP relates to disease risk, severity, and Th1 and Th17 differentiation in Parkinson's disease

Yang

Zhuang

Cai

et al. 2021

Ann Clin Transl Neurol

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“…For instance, DUSP1 deficiency promotes inflammation and bone destruction in collagen‐induced arthritis 18 ; besides, DUSP5 represses autoimmune arthritis by regulating Th17/Treg balance and inactivating osteoclastogenesis in mice 19 . In aspect of DUSP22, although no experimental study been reported, two clinical studies revealed that circulating DUSP22 is closely involved in RA risk and progression 20,21 . In our present study, we observed that synovium DUSP22 level was decreased in RA patients compared knee trauma patients; furthermore, serum DUSP22 level was also reduced in RA patients compared to knee trauma patients and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…Dual specificity phosphatase (DUSP) family has attracted great attention in terms of their regulation of immunology, inflammation, or related bioprocess of autoimmune disease including RA. 18 , 19 , 20 , 21 For instance, DUSP1 deficiency promotes inflammation and bone destruction in collagen‐induced arthritis 18 ; besides, DUSP5 represses autoimmune arthritis by regulating Th17/Treg balance and inactivating osteoclastogenesis in mice. 19 In aspect of DUSP22, although no experimental study been reported, two clinical studies revealed that circulating DUSP22 is closely involved in RA risk and progression.…”

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

Clinical Laboratory Analysis

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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.

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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

Clinical Laboratory Analysis

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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.

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JNK pathway‐associated phosphatase associates with rheumatoid arthritis risk, disease activity, and its longitudinal elevation relates to etanercept treatment response

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 9 publications

References 27 publications

JKAP relates to disease risk, severity, and Th1 and Th17 differentiation in Parkinson's disease

JKAP relates to disease risk, severity, and Th1 and Th17 differentiation in Parkinson's disease

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

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

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