{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T20:43:09Z","timestamp":1793479389917,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify a panel of serum biomarkers that could specifically identify imminent cases of rheumatoid arthritis (RA) before diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum samples were collected at 4 time points from active component US military personnel, including 157 anti\u2013citrullinated protein antibody (ACPA)\u2013seropositive and 50 ACPA\u2010seronegative RA subjects, 100 reactive arthritis (ReA) subjects, and 76 healthy controls. The cohorts were split into 2 phases, with samples tested on independent proteomic platforms for each phase. Classification models of RA diagnosis based on samples obtained within 6 months prior to diagnosis were developed both in univariate analyses and by multivariate random forest modeling of training sample sets and testing sample sets from each phase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increases in serum analytes, including C\u2010reactive protein levels, serum amyloid A, and soluble programmed cell death 1 (PD\u20101), were observed in seropositive RA subjects at the time point closest to diagnosis, up to several years before diagnosis. Only a small fraction of RA subjects had levels above the 95th percentile of healthy control levels until the time period within 6 months of diagnosis. For classification of RA diagnosis using samples obtained within 6 months prior to diagnosis, soluble PD\u20101 provided superior specificity compared to ReA cases (&gt;89%), with a sensitivity of 48% for RA classification. An 8\u2010analyte model provided superior sensitivity (69%), with comparable specificity relative to ReA (&gt;82%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate that imminent RA diagnosis could be classified with high specificity, relative to healthy controls and ReA cases, using a panel of cytokines measured in serum samples collected within 6 months before actual diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42260","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T14:29:08Z","timestamp":1654612148000},"page":"1766-1775","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Serologic Biomarkers of Progression Toward Diagnosis of Rheumatoid Arthritis in Active Component Military Personnel"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8609-118X","authenticated-orcid":false,"given":"Matthew J.","family":"Loza","sequence":"first","affiliation":[{"name":"Immunology, Janssen Research &amp; Development  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Nagpal","sequence":"additional","affiliation":[{"name":"Immunology, Janssen Research &amp; Development  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Cole","sequence":"additional","affiliation":[{"name":"Immunology, Janssen Research &amp; Development  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee M.","family":"Laird","sequence":"additional","affiliation":[{"name":"Henry M. Jackson Foundation for Military Medicine  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Alcala","sequence":"additional","affiliation":[{"name":"Henry M. Jackson Foundation for Military Medicine  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navin L.","family":"Rao","sequence":"additional","affiliation":[{"name":"Immunology, Janssen Research &amp; Development  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Riddle","sequence":"additional","affiliation":[{"name":"Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland, Reno\u2010School of Medicine, University of Nevada, and VA Sierra Nevada Health Care System  Reno Nevada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad K.","family":"Porter","sequence":"additional","affiliation":[{"name":"Enteric Diseases Department, Naval Medical Research Center  Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00077"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-010-1638-5"},{"key":"e_1_2_7_4_1","first-page":"1","article-title":"Early rheumatoid arthritis\u2014is there a window of opportunity?","volume":"80","author":"Cush JJ","year":"2007","journal-title":"J Rheumatol Suppl"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.142729"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2015.364"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq424"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27638"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780311004"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201505"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24350"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41091"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27186"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.040659"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192704"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conctc.2020.100522"},{"key":"e_1_2_7_18_1","first-page":"18","article-title":"Classification and Regression by randomForest","volume":"2","author":"Liaw A","year":"2002","journal-title":"R News"},{"key":"e_1_2_7_19_1","article-title":"Caret package","volume":"285","author":"Kuhn M.","year":"2008","journal-title":"J Stat Softw"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4540"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20810"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2013.823517"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303737200"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3848"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150784"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3260"}],"container-title":["Arthritis &amp; 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