Abstract
Objective
This study aimed to investigate the correlation of Jun N-terminal kinase pathway associated phosphatase (JKAP) with inflammation, disease activity, and clinical efficacy to triple conventional disease-modifying anti-rheumatic drugs (cDMARDs) in rheumatoid arthritis (RA) patients.
Methods
A total of 119 active RA patients about to receive triple cDMARDs treatment were enrolled. Serum JKAP was detected by enzyme-linked immunosorbent assay at week0, week6, week12, and week24 (W24). According to clinical response status or remission status at W24, RA patients were classified as response patients and non-response patients, or remission patients and non-remission patients, respectively.
Results
JKAP was negatively correlated with erythrocyte sedimentation rate (ESR), C-reactive protein, and 28-joints disease activity score based on ESR (DAS28 score (ESR)), while JKAP was not correlated with disease duration, tender joint count, swollen joint count, health assessment questionnaire for rheumatoid arthritis or treatment history. Furthermore, during 24-week triple cDMARDs treatment, JKAP was increased overtime. Subgroup analyses showed that JKAP displayed a rising trend in response patients, remission patients, non-remission patients but not non-response patients, meanwhile its increment was more obvious in remission patients versus non-remission patients. Additionally, JKAP at W24 was higher in response patients compared with non-response patients, and JKAP at W12 and W24 was higher in remission patients compared with non-remission patients.
Conclusion
Longitudinal monitor of JKAP might reflect clinical efficacy to the treatment of triple cDMARDs, which could improve outcomes in RA patients.
Similar content being viewed by others
References
Aletaha D, Smolen JS (2018) Diagnosis and management of rheumatoid arthritis: a review. JAMA 320:1360–1372
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581
Allen A, Carville S, McKenna F, Guideline Development G (2018) Diagnosis and management of rheumatoid arthritis in adults: summary of updated NICE guidance. BMJ 362:k3015
Chen AJ, Zhou G, Juan T, Colicos SM, Cannon JP, Cabriera-Hansen M, Meyer CF, Jurecic R, Copeland NG, Gilbert DJ, Jenkins NA, Fletcher F, Tan TH, Belmont JW (2002) The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway. J Biol Chem 277:36592–36601
Chuang HC, Chen YM, Hung WT, Li JP, Chen DY, Lan JL, Tan TH (2016) Downregulation of the phosphatase JKAP/DUSP22 in T cells as a potential new biomarker of systemic lupus erythematosus nephritis. Oncotarget 7:57593–57605
Hu H, Luan L, Yang K, Li SC (2018) Burden of rheumatoid arthritis from a societal perspective: A prevalence-based study on cost of this illness for patients in China. Int J Rheum Dis 21:1572–1580
Li JP, Yang CY, Chuang HC, Lan JL, Chen DY, Chen YM, Wang X, Chen AJ, Belmont JW, Tan TH (2014) The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck. Nat Commun 5:3618
Ma K, Li L, Liu C, Zhou L, Zhou X (2019) Efficacy and safety of various anti-rheumatic treatments for patients with rheumatoid arthritis: a network meta-analysis. Arch Med Sci 15:33–54
Shi X, Yang W, Wang N, Zhu J (2019) Circulating JNK pathway-associated phosphatase level correlates with decreased risk, activity, inflammation level and reduced clinical response to tumor necrosis factor-alpha inhibitor in Crohn disease patients. Medicine (Baltimore) 98:e16622
Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet 388:2023–2038
Sparks JA (2019) Rheumatoid Arthritis. Ann Intern Med 170:ITC1–ITC16
van Gestel AM, Prevoo ML, van 't Hof MA, van Rijswijk MH, van de Putte LB & van Riel PL (1996) Development and validation of the European league against rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American college of rheumatology and the world health organization/International league against rheumatism criteria. Arthritis Rheum 39: 34–40
Zhou R, Chang Y, Liu J, Chen M, Wang H, Huang M, Liu S, Wang X, Zhao Q (2017) JNK Pathway-associated phosphatase/DUSP22 suppresses CD4(+) T-Cell activation and Th1/Th17-cell differentiation and negatively correlates with clinical activity in inflammatory bowel disease. Front Immunol 8:781
Acknowledgements
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
All authors declare that there is no conflict of interest.
Research involving human participants and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Song, D., Zhu, X., Wang, F. et al. Longitudinal monitor of Jun N-terminal kinase pathway associated phosphatase reflects clinical efficacy to triple conventional disease-modifying anti-rheumatic drugs treatment in rheumatoid arthritis patients. Inflammopharmacol 29, 1131–1138 (2021). https://doi.org/10.1007/s10787-021-00823-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-021-00823-w