{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:50:27Z","timestamp":1788951027877,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["2022YFC2504600\/3\/4"],"award-info":[{"award-number":["2022YFC2504600\/3\/4"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008235","name":"Peking Union Medical College Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008235","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2025,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Neutrophil activation plays a crucial role in the pathogenesis of rheumatoid arthritis (RA), but its involvement in RA\u2010associated interstitial lung disease (RA\u2010ILD) remains unclear. This study investigated the involvement of\n N<\/jats:italic>\n \u2010formyl methionine (fMET) and its receptor formyl peptide receptor\u20101 (FPR1) in neutrophil\u2010mediated inflammation in RA\u2010ILD.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Plasma and sputum levels of fMET and neutrophil activation markers were measured by ELISA in two cohorts (\n n<\/jats:italic>\n \u00a0=\u00a0269 and 314) spanning multiple disease subgroups. Neutrophil activation was assessed by flow cytometry following plasma stimulation, with or without FPR1 inhibitors.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Calprotectin levels were significantly elevated in both plasma and sputum of RA\u2010ILD patients compared to controls and RA\u2010noILD patients (\n p\u00a0<\/jats:italic>\n <\u00a00.05 for all analyses) and were negatively correlated with pulmonary function in RA (forced vital capacity [FVC],\n r<\/jats:italic>\n \u00a0=\u00a0\u22120.39,\n p\u00a0<\/jats:italic>\n =\u00a00.0002; diffusing capacity for carbon monoxide [DLCO],\n r<\/jats:italic>\n \u00a0=\u00a0\u22120.39,\n p\u00a0<\/jats:italic>\n =\u00a00.001). Plasma fMET levels were higher in RA\u2010ILD patients compared to healthy controls (\n p<\/jats:italic>\n \u00a0<\u00a00.0001) as well as compared to RA\u2010noILD patients (\n p\u00a0<\/jats:italic>\n <\u00a00.01), with a significant inverse correlation to pulmonary function in RA patients (FVC,\n r<\/jats:italic>\n \u00a0=\u00a0\u22120.42,\n p\u00a0<\/jats:italic>\n <\u00a00.0001; DLCO,\n r<\/jats:italic>\n \u00a0=\u00a0\u22120.31,\n p\u00a0<\/jats:italic>\n =\u00a00.01). Plasma from RA\u2010ILD patients induced neutrophil activation through FPR1\u2010dependent mechanisms (\n p\u00a0<\/jats:italic>\n <\u00a00.0001). Hierarchical clustering identified reproducible subgroups defined by fMET and calprotectin, with the high\u2010fMET cluster enriched for RA\u2010ILD and associated with lower DLCO (\n p\u00a0<\/jats:italic>\n <\u00a00.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The fMET\u2013FPR1 axis is associated with neutrophil activation in RA\u2010ILD and defines inflammatory endotypes associated with lung impairment. Neutrophil\u2010based biomarkers may enable early risk stratification and provide rationale for targeting the fMET\u2013FPR1 axis in RA\u2010ILD.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/joim.70030","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T06:34:55Z","timestamp":1760510095000},"page":"656-669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Systemic neutrophil activation and\n N<\/i>\n \u2010formyl methionine\u2010formyl peptide receptor\u20101 signaling define inflammatory endotypes in rheumatoid arthritis\u2010associated lung involvement"],"prefix":"10.1111","volume":"298","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3995-6697","authenticated-orcid":false,"given":"Jia","family":"Shi","sequence":"first","affiliation":[{"name":"Division of Rheumatology University of Washington Seattle Washington USA"},{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science & Technology Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Key Laboratory of Rheumatology and Clinical Immunology Ministry of Education Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science & Technology Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Key Laboratory of Rheumatology and Clinical Immunology Ministry of Education Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Shunyi District Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueting","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science & Technology Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Key Laboratory of Rheumatology and Clinical Immunology Ministry of Education Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyun","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science & Technology Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Key Laboratory of Rheumatology and Clinical Immunology Ministry of Education Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0650-7713","authenticated-orcid":false,"given":"Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of Washington Seattle Washington USA"},{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science & Technology Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Key Laboratory of Rheumatology and Clinical Immunology Ministry of Education Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Stultz","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Shunyi District Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science & Technology Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Key Laboratory of Rheumatology and Clinical Immunology Ministry of Education Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4252-2889","authenticated-orcid":false,"given":"Mengtao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science & Technology Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Key Laboratory of Rheumatology and Clinical Immunology Ministry of Education Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4541-9898","authenticated-orcid":false,"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science & Technology Beijing China"},{"name":"State Key Laboratory of Common Mechanism Research for Major Diseases Key Laboratory of Rheumatology and Clinical 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Kristen","family":"Demoruelle","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of Colorado Denver Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Solomon","sequence":"additional","affiliation":[{"name":"National Jewish Health Center for Interstitial Lung Disease Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6171-1952","authenticated-orcid":false,"given":"Christian","family":"Lood","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of Washington Seattle Washington 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