{
    "abstract": "Carbamylated proteins and dysregulated neutrophils are implicated in rheumatoid arthritis (RA) pathogenesis. Herein, we characterized the neutrophils present in RA synovial fluid (SF) using proteomic techniques and evaluated their contribution to protein carbamylation.\nRA-SF neutrophil proteomic profile and SF proteome signature were investigated using high-resolution mass spectrometry. Carbamylated proteins and the degree of protein carbamylation were evaluated by mass spectrometric analysis. ELISA and chemiluminescence kits were used to examine myeloperoxidase (MPO) activity, and hydrogen peroxide (H\nSF neutrophils exhibited a shift in proteomic cargo with up-regulated proteins involved in defense responses, neutrophil degranulation, and reactive oxygen species metabolic processes, while proteins down-regulated were associated with megakaryocyte differentiation, leukocyte migration, and integrin-mediated signaling pathway. Elevated levels of neutrophil-derived proteins were detected in RA-SF. In addition, we specifically identified many carbamylated proteins and observed an increased frequency of protein carbamylation in RA-SF samples. Functionally, neutrophils from RA-SF showed a significantly increased level of MPO release and HH\nSynovial neutrophils were found to be activated and increased releasing protein cargo, including MPO and ROS, into the synovial fluid. Presence of many carbamylated proteins in RA-SF and an increased MPO activity showed a strong correlation to the degree of protein carbamylation, suggesting neutrophil-derived MPO in promoting generation of aberrantly carbamylated proteins.",
    "authors": [
        {
            "affiliation": "Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.",
            "firstname": "Xueting",
            "initials": "X",
            "lastname": "Chen"
        },
        {
            "affiliation": "Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.",
            "firstname": "Rong",
            "initials": "R",
            "lastname": "Du"
        },
        {
            "affiliation": "Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.",
            "firstname": "Pan",
            "initials": "P",
            "lastname": "Wang"
        },
        {
            "affiliation": "Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.",
            "firstname": "WenLin",
            "initials": "W",
            "lastname": "Qiu"
        },
        {
            "affiliation": "Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.",
            "firstname": "Lu",
            "initials": "L",
            "lastname": "Chen"
        },
        {
            "affiliation": "Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.",
            "firstname": "Jian",
            "initials": "J",
            "lastname": "Wan"
        },
        {
            "affiliation": "Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.",
            "firstname": "Hui",
            "initials": "H",
            "lastname": "Qiu"
        },
        {
            "affiliation": "Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.",
            "firstname": "Li",
            "initials": "L",
            "lastname": "Xiong"
        },
        {
            "affiliation": "Department of Environmental and Biosciences, School of Business, Innovation and Sustainability, Halmstad University, Halmstad, Sweden.",
            "firstname": "Kutty Selva",
            "initials": "KS",
            "lastname": "Nandakumar"
        },
        {
            "affiliation": "Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.\nNational-Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, China.",
            "firstname": "Rikard",
            "initials": "R",
            "lastname": "Holmdahl"
        },
        {
            "affiliation": "Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.",
            "firstname": "Hui",
            "initials": "H",
            "lastname": "Geng"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025 Chen, Du, Wang, Qiu, Chen, Wan, Qiu, Xiong, Nandakumar, Holmdahl and Geng.",
    "doi": "10.3389/fimmu.2025.1563426\n10.1073/pnas.1114465108\n10.1136/annrheumdis-2019-216709\n10.4049/jimmunol.1000075\n10.1002/art.37830\n10.1136/annrheumdis-2015-207326\n10.1126/scitranslmed.3005218\n10.1053/j.ajkd.2014.04.034\n10.1038/nm1637\n10.1074/jbc.M117.801076\n10.1042/bj3270487\n10.1021/pr500030x\n10.1089/ars.2011.4403\n10.55563/clinexprheumatol/0ms5pk\n10.1136/annrheumdis-2016-210772\n10.1038/nrrheum.2014.80\n10.1038/s41577-022-00787-0\n10.1002/art.39313\n10.1126/scitranslmed.3005580\n10.1189/jlb.1212619\n10.1371/journal.ppat.1000639\n10.1002/art.38299\n10.1042/bj2500081\n10.1093/rheumatology/kes193\n10.1038/nmeth.1322\n10.1038/nprot.2016.136\n10.1002/eji.201444869\n10.1016/j.jbc.2022.101832\n10.1016/j.jaut.2017.02.008\n10.3389/fimmu.2020.584116\n10.1136/ard.2004.034132\n10.1002/art.v48:10\n10.1136/ard.52.5.354\n10.1136/annrheumdis-2021-221866\n10.1111/j.1365-2567.2006.02471.x\n10.1182/blood-2007-10-116285\n10.3389/fimmu.2014.00448\n10.1186/ar4579\n10.1016/j.celrep.2019.10.082\n10.1038/ni.3693\n10.1136/ard.2006.064741\n10.1002/art.v50:12\n10.1186/s12014-020-09292-9\n10.1093/rheumatology/ken412\n10.1038/nm1638\n10.1002/art.40098\n10.1073/pnas.1517096113\n10.1038/s41598-019-54817-4\n10.3390/ijms21218057\n10.1016/j.autrev.2013.10.008\n10.1126/sciadv.abd2688\n10.1080/14397595.2019.1583819\n10.1186/s13075-017-1455-1\n10.1136/annrheumdis-2014-206797\n10.1136/annrheumdis-2016-210059\n10.1038/s41584-019-0244-4",
    "journal": "Frontiers in immunology",
    "keywords": [
        "carbamylation",
        "myeloperoxidase",
        "neutrophil",
        "rheumatoid arthritis",
        "synovial fluid"
    ],
    "methods": null,
    "publication_date": "2025-04-24",
    "pubmed_id": "40270967\n21987802\n32156708\n20488785\n23279976\n26443608\n23467560\n25037561\n17828273\n29496995\n9359420\n24724574\n22462773\n32896247\n28442530\n24914698\n36257987\n26245941\n23536012\n23650620\n19876394\n24757143\n2833238\n22814531\n19377485\n27809316\n17937476\n25130613\n35304099\n28291659\n33469455\n15778239\n14558085\n8100700\n35168946\n17034427\n18669870\n25285096\n24928093\n31747616\n28263321\n17234650\n15593230\n32782445\n19029133\n17767165\n28296337\n26712018\n31797985\n33137905\n24176675\n33115748\n30789095\n29096669\n25653200\n28183721\n31253945",
    "results": "SF neutrophils exhibited a shift in proteomic cargo with up-regulated proteins involved in defense responses, neutrophil degranulation, and reactive oxygen species metabolic processes, while proteins down-regulated were associated with megakaryocyte differentiation, leukocyte migration, and integrin-mediated signaling pathway. Elevated levels of neutrophil-derived proteins were detected in RA-SF. In addition, we specifically identified many carbamylated proteins and observed an increased frequency of protein carbamylation in RA-SF samples. Functionally, neutrophils from RA-SF showed a significantly increased level of MPO release and HH",
    "title": "Proteomic analysis of infiltrating neutrophils from rheumatoid arthritis synovial fluid and their contribution to protein carbamylation.",
    "xml": "<Element 'PubmedArticle' at 0x78850427f8d0>"
}