{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:49:57Z","timestamp":1780336197724,"version":"3.54.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871242"],"award-info":[{"award-number":["81871242"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease. Given its rapid disease progression and high mortality rate, early warning is crucial in improving the outcomes, However, to date, relevant comprehensive predictors or an effective prediction model are still poorly explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A plasma proteomic profile was performed at early stages in patients with SFTS. Functional clustering analysis was used to select the candidate proteins and then validate their expression by ELISA. A cohort consisting of 190 patients with SFTS was used to develop the predictive model for severe illness and subsequently validate it in a new cohort consisting of 93 patients with SFTS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significant increase in plasma proteins associated with various functional clusters, such as the proteasomal protein catabolic process, phagocytosis, and humoral immune response, was observed in severe SFTS patients. High levels of four proteins including NID1, HSP90\u03b1, PSMA1, and VCAM1 were strongly correlated with multi-organ damage and disease progression. A prediction model was developed at the early stage to accurately predict severe conditions with the area under the curve of 0.931 (95% CI, 0.885, 0.963).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The proteomic signatures identified in this study provide insights into the potential pathogenesis of SFTS. The predictive models have substantial clinical implications for the early identification of SFTS patients who may progress to severe conditions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1514388","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T07:37:53Z","timestamp":1738741073000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of early prediction biomarkers of severity in patients with severe fever with thrombocytopenia syndrome based on plasma proteomics"],"prefix":"10.3389","volume":"16","author":[{"given":"Qian","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luchen","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3389\/fimmu.2016.00159","article-title":"Extracellular HSPs: the complicated roles of extracellular HSPs in immunity","volume":"7","author":"Calderwood","year":"2016","journal-title":"Front. Immunol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3969\/j.issn.1007-8134.2022.05.001","article-title":"Expert consensus on diagnosis and treatment of severe fever with thrombocytopenia syndrome","volume":"35","author":"Chen","year":"2022","journal-title":"Infect. Dis. Inform."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s40249-022-01017-4","article-title":"Transmission and mortality risk assessment of severe fever with thrombocytopenia syndrome in China: results from 11-years\u2019 study","volume":"11","author":"Chen","year":"","journal-title":"Infect. Dis. Poverty"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"852","DOI":"10.3760\/cma.j.cn112338-20220325-00228","article-title":"Epidemiological characteristics of severe fever with thtrombocytopenia syndrome in China, 2011\u20132021","volume":"43","author":"Chen","year":"","journal-title":"Chin. J. Epidemiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/rmv.1725","article-title":"The ubiquitin-proteasome system in positive-strand RNA virus infection","volume":"23","author":"Choi","year":"2013","journal-title":"Rev. Med. Virol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jinf.2014.08.001","article-title":"Severe fever with thrombocytopenia syndrome bunyavirus-related human encephalitis","volume":"70","author":"Cui","year":"2015","journal-title":"J. Infect."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3760\/cma.j.issn.0578-1426.2012.10.005","article-title":"The clinical characteristics of 169 cases of severe fever with thrombocytopenia syndrome","volume":"51","author":"Cui","year":"2012","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"O870","DOI":"10.1111\/1469-0691.12636","article-title":"Prognostic value of clinical and immunological markers in acute phase of SFTS virus infection","volume":"20","author":"Ding","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1093\/infdis\/jis472","article-title":"Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients","volume":"206","author":"Gai","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1186\/s12879-021-06946-3","article-title":"Clinical features of severe fever with thrombocytopenia syndrome and analysis of risk factors for mortality","volume":"21","author":"He","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1111\/pin.12207","article-title":"Two autopsy cases of severe fever with thrombocytopenia syndrome (SFTS) in Japan: a pathognomonic histological feature and unique complication of SFTS","volume":"64","author":"Hiraki","year":"2014","journal-title":"Pathol. Int."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.3390\/ijms19092560","article-title":"The HSP90 family: structure, regulation, function, and implications in health and disease","volume":"19","author":"Hoter","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e0133622","DOI":"10.1128\/jvi.01336-22","article-title":"Human cytomegalovirus utilizes multiple viral proteins to regulate the basement membrane protein nidogen 1","volume":"96","author":"Kuan","year":"2022","journal-title":"J. Virol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jcv.2018.01.017","article-title":"Kinetics of viral load and cytokines in severe fever with thrombocytopenia syndrome","volume":"101","author":"Kwon","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12014-022-09368-8","article-title":"Serum proteomics of severe fever with thrombocytopenia syndrome patients","volume":"19","author":"Lee","year":"2022","journal-title":"Clin. Proteomics"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/S1473-3099(18)30293-7","article-title":"Epidemiological and clinical features of laboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011\u20132017: a prospective observational study","volume":"18","author":"Li","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"711","DOI":"10.3760\/cma.j.cn311365-20221017-00425","article-title":"Consensus on the diagnosis and treatment of severe fever with thrombocytopenia syndrome","volume":"40","author":"Li","year":"2022","journal-title":"Chin. J. Infect. Dis."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e0005746","DOI":"10.1371\/journal.pntd.0005746","article-title":"Endothelial activation and dysfunction in severe fever with thrombocytopenia syndrome","volume":"11","author":"Li","year":"2017","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.virol.2018.05.001","article-title":"Vascular endothelial injury in severe fever with thrombocytopenia syndrome caused by the novel bunyavirus","volume":"520","author":"Li","year":"2018","journal-title":"Virology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/S1473-3099(14)70718-2","article-title":"Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis","volume":"14","author":"Liu","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1128\/JVI.02277-13","article-title":"The pathogenesis of severe fever with thrombocytopenia syndrome virus infection in alpha\/beta interferon knockout mice: insights into the pathologic mechanisms of a new viral hemorrhagic fever","volume":"88","author":"Liu","year":"2014","journal-title":"J. Virol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1093\/infdis\/jiad196","article-title":"Association of deforestation with severe fever with thrombocytopenia syndrome","volume":"228","author":"Nam","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.1128\/JVI.02191-07","article-title":"Regulation of immune response and inflammatory reactions against viral infection by VCAM-1","volume":"82","author":"Ou","year":"2008","journal-title":"J. Virol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.ijid.2015.12.009","article-title":"Decreased monocyte subsets and TLR4-mediated functions in patients with acute severe fever with thrombocytopenia syndrome (SFTS)","volume":"43","author":"Peng","year":"2016","journal-title":"Int. J. Infect. Dis."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3477","DOI":"10.1002\/pmic.200400897","article-title":"The use of proteomics in the discovery of serum biomarkers from patients with severe acute respiratory syndrome","volume":"4","author":"Ren","year":"2004","journal-title":"Proteomics"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e0114219","DOI":"10.1128\/JVI.01142-19","article-title":"Heat shock protein 90 ensures the integrity of rubella virus p150 protein and supports viral replication","volume":"93","author":"Sakata","year":"2019","journal-title":"J. Virol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/j.immuni.2020.10.008","article-title":"Plasma proteomics identify biomarkers and pathogenesis of COVID-19","volume":"53","author":"Shu","year":"2020","journal-title":"Immunity"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1007\/s10096-022-04506-4","article-title":"Analysis of risk factors associated with fatal outcome among severe fever with thrombocytopenia syndrome patients from 2015 to 2019 in Shandong, China","volume":"41","author":"Song","year":"2022","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1093\/infdis\/jis452","article-title":"Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome","volume":"206","author":"Sun","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/bies.950180208","article-title":"Supramolecular assembly of basement membranes","volume":"18","author":"Timpl","year":"1996","journal-title":"BioEssays"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1007\/s00705-019-04306-w","article-title":"Changes to virus taxonomy and the international code of virus classification and nomenclature ratified by the international committee on taxonomy of viruses (2019)","volume":"164","author":"Walker","year":"2019","journal-title":"Arch. Virol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e0255033","DOI":"10.1371\/journal.pone.0255033","article-title":"Application of a decision tree model in the early identification of severe patients with severe fever with thrombocytopenia syndrome","volume":"16","author":"Wang","year":"2021","journal-title":"PLoS One"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e0010489","DOI":"10.1371\/journal.pntd.0010489","article-title":"Clinical laboratory parameters and fatality of severe fever with thrombocytopenia syndrome patients: a systematic review and meta-analysis","volume":"16","author":"Wang","year":"2022","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e0007829","DOI":"10.1371\/journal.pntd.0007829","article-title":"A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome at the early stage-a multicenter study in China","volume":"13","author":"Wang","year":"2019","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e0129422","DOI":"10.1128\/spectrum.01294-22","article-title":"Mast cell-derived proteases induce endothelial permeability and vascular damage in severe fever with thrombocytopenia syndrome","volume":"10","author":"Wang","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"6754","DOI":"10.1073\/pnas.1817867116","article-title":"Multiplex targeted mass spectrometry assay for one-shot flavivirus diagnosis","volume":"116","author":"Wee","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e02246","DOI":"10.1128\/JVI.02246-17","article-title":"RIG-I-like receptor and Toll-like receptor signaling pathways cause aberrant production of inflammatory cytokines\/chemokines in a severe fever with thrombocytopenia syndrome virus infection mouse model","volume":"92","author":"Yamada","year":"2018","journal-title":"J. Virol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3892\/ijmm.2022.5174","article-title":"Overview of the immunological mechanism underlying severe fever with thrombocytopenia syndrome (review)","volume":"50","author":"Yang","year":"2022","journal-title":"Int. J. Mol. Med."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/S1473-3099(18)30312-8","article-title":"Risk factors for death in severe fever with thrombocytopenia syndrome","volume":"18","author":"Yu","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1056\/NEJMoa1010095","article-title":"Fever with thrombocytopenia associated with a novel bunyavirus in China","volume":"364","author":"Yu","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1093\/infdis\/jiae039","article-title":"Identification of CCL20 as a prognostic predictor for severe fever with thrombocytopenia syndrome based on plasma proteomics","volume":"230","author":"Zhang","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.ijid.2022.10.008","article-title":"Fatal patients with severe fever with thrombocytopenia syndrome in China","volume":"125","author":"Zhao","year":"2022","journal-title":"Int. J. Infect. 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