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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1436193
This article is part of the Research Topic Innate immune dysregulation: a driving force of autoimmunity and chronic inflammation View all 4 articles

Increased Neutrophil Extracellular Trap Formation in Oligoarticular, Polyarticular Juvenile Idiopathic Arthritis and Enthesitis-Related Arthritis: Biomarkers for Diagnosis and Disease Activity

Provisionally accepted
Hongxia Tang Hongxia Tang 1Yucheng Zhong Yucheng Zhong 2Wu Yali Wu Yali 3*Yanmei Huang Yanmei Huang 4*Yi Liu Yi Liu 3*Jing Chen Jing Chen 3*Ting Xi Ting Xi 3*Yini Wen Yini Wen 3*Ting He Ting He 3*Shanshan Yang Shanshan Yang 3*Fan Liu Fan Liu 3*Runji Xiong Runji Xiong 1*Runming Jin Runming Jin 1*
  • 1 Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 2 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • 3 Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
  • 4 Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

The final, formatted version of the article will be published soon.

    Objective. Neutrophil extracellular traps (NETs) are important factors in initiating and perpetuating inflammation. However, the role of NETs in different subtypes of juvenile idiopathic arthritis (JIA) has been rarely studied. Therefore, we aimed to explore the ability of JIA-derived neutrophils to release NETs and the effect of TNF-α (tumor necrosis factor-alpha) inhibitors on NET formation both in vitro and in vivo, and evaluate the associations of NET-derived products with clinical and immunerelated parameters.Methods. The ability of neutrophils to release NETs and the effect of adalimumab on NET formation was assessed via in vitro stimulation and inhibition studies. Plasma NET-derived products were detected to assess the incidence of NET formation in vivo.Furthermore, flow cytometry and western blotting were used to detect NET-associated signaling components in neutrophils.Results. Compared to those derived from HCs, neutrophils derived from patients with oligoarticular-JIA, polyarticular-JIA and enthesitis-related arthritis were more prone to generate NETs spontaneously and in response to TNF-α or PMA in vitro.Excessive NET formation existed in peripheral circulation of JIA patients, and elevated plasma levels of NET-derived products (cell-free DNA and MPO-DNA complexes) could accurately distinguish JIA patients from HCs and were positively correlated with

    Keywords: juvenile idiopathic arthritis, Neutrophils, neutrophil extracellular traps, biomarkers, Tumor Necrosis Factor-alpha

    Received: 21 May 2024; Accepted: 23 Jul 2024.

    Copyright: © 2024 Tang, Zhong, Yali, Huang, Liu, Chen, Xi, Wen, He, Yang, Liu, Xiong and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Wu Yali, Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
    Yanmei Huang, Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
    Yi Liu, Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
    Jing Chen, Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
    Ting Xi, Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
    Yini Wen, Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
    Ting He, Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
    Shanshan Yang, Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
    Fan Liu, Department of Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
    Runji Xiong, Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Runming Jin, Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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