{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:40:30Z","timestamp":1792208430570,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7252264"],"award-info":[{"award-number":["7252264"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574850"],"award-info":[{"award-number":["82574850"]}],"id":[{"id":"10.13039\/501100001809","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>Pathologic bone formation in ankylosing spondylitis (AS) is not fully reflected by systemic inflammation, limiting the utility of markers of inflammation for structural damage assessment. This study aimed to identify plasma protein signatures associated with structural damage severity in AS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Deep plasma proteomics was conducted in a prospective 88\u2010participant discovery cohort comprising 25 and 31 patients with high and low structural damage, respectively, stratified by the Spondyloarthritis Research Consortium of Canada sacroiliac joint structural score and 32 normal controls. Age\u2010 and sex\u2010adjusted differential expression analysis, weighted gene coexpression network analysis (WGCNA), and integrated machine learning were used to characterize damage\u2010associated molecular programs and prioritize biomarkers. Five candidate proteins were validated by enzyme\u2010linked immunosorbent assay in an independent 88\u2010participant cohort (32 high, 32 low, and 24 normal controls).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Proteomic profiling identified 536 differentially expressed proteins between the high structural damage group and normal controls. WGCNA revealed a structural\u2010damage\u2013associated module, enriched in platelet activation and cell\u2013matrix adhesion, together with an AS\u2010associated reduction in a module related to RNA processing and translation. Integrated analysis prioritized a five\u2010protein signature comprising ITGA2B, HSPG2, ITGB1, EPHB2, and SAA2. The combined model achieved an area under the curve (AUC) of 0.917 in the validation cohort and significantly outperformed individual biomarkers (AUCs 0.732\u20130.819; all Holm\u2010adjusted\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study supports a dual\u2010pathway model in which SAA2\u2010marked systemic inflammation and ITGA2B\u2010associated platelet\u2013extracellular matrix remodeling appear partially dissociated yet remain biologically interconnected in AS. The validated five\u2010protein panel provides a noninvasive tool for identifying patients with current high structural damage that complements imaging\u2010based assessment by capturing biologic heterogeneity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70353","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T10:02:28Z","timestamp":1790589748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Proteomics Identifies Molecular Signatures and Biomarkers Associated With High Structural Damage in Ankylosing Spondylitis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1899-3167","authenticated-orcid":false,"given":"Tiantian","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4116-2597","authenticated-orcid":false,"given":"Wanlin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Guang'anmen Hospital (Jinan) China Academy of Chinese Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinning","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60635-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00625-y"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31591-4"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406182"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2025.120533"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key128"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(25)00108-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.066415"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080871"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41206"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1665-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215356"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.258"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-024-02002-9"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-014-2663-6"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/ORR.S540714"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-026-00744-w"},{"issue":"6","key":"e_1_2_8_19_1","first-page":"7272","article-title":"Up\u2010regulation of soluble P\u2010selectin predicates its prognostic value in patients with ankylosing spondylitis","volume":"8","author":"Zhou X","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2021-001751"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-023-03142-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4751"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2024.100900"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.70020"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-023-03044-4"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270401"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.108233"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.140519"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21337"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-022-05609-x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2007.48.2.218"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S310677"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.12.010"},{"issue":"5","key":"e_1_2_8_34_1","first-page":"752","article-title":"Serum amyloid A activates nuclear factor\u2010kappaB in rheumatoid synovial fibroblasts through binding to receptor of advanced glycation end\u2010products","volume":"35","author":"Okamoto H","year":"2008","journal-title":"J Rheumatol"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315583"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.202309"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2536-7"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.112163"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.9"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.856261"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi1005199"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.05.052"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56513-6"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202404768"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.598612"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.20888"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.140555"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-024-00308-0"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02993-x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-023-04200-x"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70353","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.70353","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70353","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:51:57Z","timestamp":1792205517000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":49,"alternative-id":["10.1002\/art.70353"],"URL":"https:\/\/doi.org\/10.1002\/art.70353","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"assertion":[{"value":"2026-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"art.70353"}}