{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:37:30Z","timestamp":1784547450250,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92374202"],"award-info":[{"award-number":["92374202"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3602000"],"award-info":[{"award-number":["2022YFC3602000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFE0131700"],"award-info":[{"award-number":["2022YFE0131700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012326","name":"International Science and Technology Cooperation Programme","doi-asserted-by":"publisher","award":["Z251100007125012"],"award-info":[{"award-number":["Z251100007125012"]}],"id":[{"id":"10.13039\/501100012326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202311030"],"award-info":[{"award-number":["SZSM202311030"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Arthralgia, an early manifestation preceding definite rheumatoid arthritis (RA), represents a critical window to identify high\u2010risk individuals and implement timely interventions. However, the immunopathologic mechanisms underlying the transition from arthralgia to established RA remain incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed a multiomics strategy integrating peripheral immune cell phenotyping, serum proteomics, and autoantibody profiling to investigate the immunopathologic continuum from preclinical to established RA. A prospective cohort of 346 patients with recent\u2010onset arthralgia was enrolled. Participants included healthy controls, self\u2010limiting arthralgia (SLA), arthralgia at risk of RA (at\u2010risk individuals, ARI), early RA, and established RA. RA development in ARI was ascertained through 24\u2010month follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with SLA, ARI showed immune dysregulation, including reduced Treg cells and a lower Treg\/Th17 cell ratio, with related changes persisting into early RA. Serum proteomics revealed upregulation of C5, \u03b1\u20101\u2010B glycoprotein, RPUSD4, WDR87, and FUBP2, which showed inverse associations with Treg cells. Autoantibody profiling identified stage\u2010specific reactivity, with ARI showing elevated antibodies against stress\u2010related proteins. Within 24 months, 18.4% of ARI progressed to RA (converters). Baseline immunophenotypic differences between converters and nonconverters were comparable, whereas longitudinal paired analyses revealed a reduction in Treg cells and Treg\/Th17 cell ratio. Treg\/Th17 cell ratio (area under the curve [AUC] 0.734) outperformed anti\u2013cyclic citrullinated peptide (CCP; AUC 0.611) in discriminating ARI from SLA, particularly in patients who are anticitrullinated peptide antibodies negative (AUC 0.729). Combining Treg cells, anti\u2010CCP and Treg\/Th17 cell ratio improved classification performance (AUC 0.783).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings delineate a critical transition from reversible immune dysregulation to established autoimmunity along the arthralgia\u2013RA continuum, suggesting that Treg cell\u2013related dysregulation may be associated with progression toward persistent inflammatory arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70194","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:51:01Z","timestamp":1776750661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrative Multiomics Approaches Identify Biomarkers Associated With Progression From Arthralgia to Rheumatoid Arthritis"],"prefix":"10.1002","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Beijing Key Laboratory of Non\u2010invasive Diagnosis and Immunotherapy of Rheumatic Diseases Peking University People's Hospital  Beijing China"},{"name":"Department of Rheumatism and Immunology, Shenzhen Key Laboratory of Inflammatory and Immunology Diseases Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipeng","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Beijing Key Laboratory of Non\u2010invasive Diagnosis and Immunotherapy of Rheumatic Diseases Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1535-8222","authenticated-orcid":false,"given":"Minghua","family":"Zhan","sequence":"additional","affiliation":[{"name":"National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing Hospital\/National Center of Gerontology  Beijing China"},{"name":"Department of Clinical Laboratory, Hebei Key Laboratory of Pathogenic Mechanisms and Diagnosis &amp; Treatment Technologies for Lung Microbiome First Affiliated Hospital of Hebei North University  Zhangjiakou Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences\u2010Beijing Beijing Institute of Lifeomics  Beijing 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