{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:39:04Z","timestamp":1783424344196,"version":"3.54.6"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"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":["31970651"],"award-info":[{"award-number":["31970651"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92046018"],"award-info":[{"award-number":["92046018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Rheumatoid arthritis (RA) causes long\u2010term functional disability, aggravating physical and mental stress to patients. However, the dynamic pathogenesis before RA onset remains unclear. Here we examined the associations between 2923 plasma proteins and incident RA in the UK Biobank cohort. Over a 15\u2010year follow\u2010up period, 433 RA cases were identified, revealing 460 significant protein\u2010RA associations. These RA\u2010related proteins were predominantly involved in immune responses, such as leukocyte migration, T cell activation, and lymphocyte activation. Sixty five proteins were significantly associated with both long\u2010term and near\u2010term risk of RA. Among them, 26 proteins exhibited changes as early as over 15\u2009years prior to RA onset with progressively fluctuating, such as IL6 and IFI30. Others, such as CDCP1 and TGFA, showed inconsistent fluctuation patterns, while proteins like GDF15 and EDA2R began to fluctuate closer to the onset of RA. Furthermore, these proteins demonstrated robust predictive performance, with an area under the curve (AUC) of 0.818 in the training set and 0.766 in the test set. When combined with demographic measures, the predictive model showed further improvement, achieving an AUC of 0.871 in the training set and 0.919 in the test set. Our findings characterise plasma protein fluctuation trajectories over 15\u2009years before RA onset and deepen our understanding of early\u2010stage pathogenesis.<\/jats:p>","DOI":"10.1111\/imm.70066","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T08:20:51Z","timestamp":1762935651000},"page":"551-561","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Plasma Protein Fluctuation Trajectories Over 15\u2009Years Before Rheumatoid Arthritis Onset"],"prefix":"10.1111","volume":"177","author":[{"given":"Chen","family":"Sun","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"She","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxian","family":"Tao","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linna","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Faculty of Information Engineering and Automation Kunming University of Science and Technology  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinduo","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Dong","sequence":"additional","affiliation":[{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"},{"name":"Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Tang","sequence":"additional","affiliation":[{"name":"The Fourth Affiliated Hospital, Zhejiang University School of Medicine  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanwu","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Shang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchao","family":"Lyu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-6554","authenticated-orcid":false,"given":"Yongshuai","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology Harbin Medical University  Harbin China"},{"name":"The Rheumatoid Arthritis Bioinformatics Center  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(24)00196-6"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-025-01589-z"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.2196\/57918"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.4103\/singaporemedj.SMJ-2023-167"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000543444"},{"issue":"9","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","DOI":"10.36660\/abc.20240252i","article-title":"Polygenic Risk Scores: The Next Step for Improved Risk Stratification in Coronary Artery Disease?","volume":"121","author":"Stein R.","year":"2024","journal-title":"Arquivos Brasileiros de Cardiologia"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/iji.12637"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07352-2"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-225306"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-025-03111-1"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03142-z"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43575-7"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121413"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-0268-2"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02840-x"},{"issue":"3","key":"e_1_2_12_17_1","article-title":"clusterProfiler 4.0: A Universal Enrichment Tool for Interpreting Omics Data","volume":"2","author":"Wu T.","year":"2021","journal-title":"Innovation"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq064"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5MB00663E"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5941"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06592-6"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-025-02248-x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00211-4"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00740-8"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.051"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70066","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.70066","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70066","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:28:37Z","timestamp":1771028917000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.70066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/imm.70066"],"URL":"https:\/\/doi.org\/10.1111\/imm.70066","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"assertion":[{"value":"2025-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}