{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:59:06Z","timestamp":1792900746210,"version":"4.5.0"},"reference-count":112,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Competitive State Research Funding of the Expert Responsibility Area of Tampere University Hospital","award":["x"],"award-info":[{"award-number":["x"]}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9lius Foundation","doi-asserted-by":"publisher","award":["x"],"award-info":[{"award-number":["x"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004155","name":"Magnus Ehrnrooth Foundation","doi-asserted-by":"publisher","award":["x"],"award-info":[{"award-number":["x"]}],"id":[{"id":"10.13039\/501100004155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006706","name":"Tampere Tuberculosis Foundation","doi-asserted-by":"publisher","award":["x"],"award-info":[{"award-number":["x"]}],"id":[{"id":"10.13039\/501100006706","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Annually, over 10,000 cases of hemorrhagic fever with renal syndrome (HFRS) are diagnosed in Europe. Puumala hantavirus (PUUV) causes most of the European HFRS cases. PUUV causes usually a relatively mild disease, which is rarely fatal. However, the severity of the infection varies greatly, and factors affecting the severity are mostly unrevealed. Host genes are known to have an effect. The typical clinical features in PUUV infection include acute kidney injury, thrombocytopenia, and increased vascular permeability. The primary target of hantavirus is the endothelium of the vessels of different organs. Although PUUV does not cause direct cytopathology of the endothelial cells, remarkable changes in both the barrier function of the endothelium and the function of the infected endothelial cells occur. Host immune or inflammatory mechanisms are probably important in the development of the capillary leakage. Several immunoinflammatory biomarkers have been studied in the context of assessing the severity of HFRS caused by PUUV. Most of them are not used in clinical practice, but the increasing knowledge about the biomarkers has elucidated the pathogenesis of PUUV infection.<\/jats:p>","DOI":"10.3390\/v14010045","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T06:55:03Z","timestamp":1640674503000},"page":"45","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Severity Biomarkers in Puumala Hantavirus Infection"],"prefix":"10.3390","volume":"14","author":[{"given":"Tuula K.","family":"Outinen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Tampere University Hospital, El\u00e4m\u00e4naukio 2, 33520 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Arvo Ylp\u00f6n katu 34, Tampere University, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-2401","authenticated-orcid":false,"given":"Satu","family":"M\u00e4kel\u00e4","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tampere University Hospital, El\u00e4m\u00e4naukio 2, 33520 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Arvo Ylp\u00f6n katu 34, Tampere University, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-7564","authenticated-orcid":false,"given":"Ilkka","family":"P\u00f6rsti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tampere University Hospital, El\u00e4m\u00e4naukio 2, 33520 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Arvo Ylp\u00f6n katu 34, Tampere University, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Vaheri","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Mustonen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tampere University Hospital, El\u00e4m\u00e4naukio 2, 33520 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Arvo Ylp\u00f6n katu 34, Tampere University, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nrmicro3066","article-title":"Uncovering the mysteries of hantavirus infections","volume":"11","author":"Vaheri","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/rmv.1722","article-title":"Hantavirus infections in Europe and their impact on public health","volume":"23","author":"Vaheri","year":"2013","journal-title":"Rev. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1473-3099(03)00774-6","article-title":"Hantavirus infections in Europe","volume":"3","author":"Vapalahti","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"18925","DOI":"10.2807\/ese.13.28.18925-en","article-title":"Situation of hantavirus infections and haemorrhagic fever with renal syndrome in European countries as of December 2006","volume":"13","author":"Heyman","year":"2008","journal-title":"Eurosurveillance"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1017\/S0950268810000087","article-title":"Disease burden of Puumala virus infections, 1995\u20132008","volume":"138","author":"Makary","year":"2010","journal-title":"Epidemiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/00365549409008583","article-title":"Nephropathia epidemica in Finland: A retrospective study of 126 cases","volume":"26","author":"Mustonen","year":"1994","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1093\/clinids\/11.6.921","article-title":"Clinical characteristics of nephropathia epidemica in Sweden: Prospective study of 74 cases","volume":"11","author":"Settergren","year":"1989","journal-title":"Rev. Infect. Dis."},{"key":"ref_8","first-page":"1","article-title":"Nephropathia epidemica in Finland. A clinical histological and epidemiological study","volume":"3","year":"1971","journal-title":"Ann. Clin. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.antiviral.2013.10.001","article-title":"The pathogenesis of nephropathia epidemica: New knowledge and unanswered questions","volume":"100","author":"Mustonen","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1093\/ndt\/gfq118","article-title":"Characterization and outcome following Puumala virus infection: A retrospective analysis of 75 cases","volume":"25","author":"Braun","year":"2010","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.3201\/eid1610.100242","article-title":"Mortality rate patterns for hemorrhagic fever with renal syndrome caused by Puumala virus","volume":"16","author":"Hjertqvist","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/ki.1996.29","article-title":"Genetic susceptibility to severe course of nephropathia epidemica caused by Puumala hantavirus","volume":"49","author":"Mustonen","year":"1996","journal-title":"Kidney Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1086\/342413","article-title":"Human leukocyte antigen-B8-DR3 is a more important risk factor for severe Puumala hantavirus infection than the tumor necrosis factor-alpha(-308) G\/A polymorphism","volume":"186","author":"Mustonen","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.thromres.2011.11.007","article-title":"Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection","volume":"129","author":"Laine","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1080\/00365540701633012","article-title":"Association of chest radiography findings with host-related genetic factors in patients with nephropathia epidemica","volume":"40","author":"Paakkala","year":"2008","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Vaheri, A., Henttonen, H., and Mustonen, J. (2021). Hantavirus Research in Finland: Highlights and Perspectives. Viruses, 13.","DOI":"10.3390\/v13081452"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1182\/blood.V86.4.1243.bloodjournal8641243","article-title":"Interleukin-6 family of cytokines and gp130","volume":"86","author":"Kishimoto","year":"1995","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.bbamcr.2011.01.034","article-title":"The pro- and anti-inflammatory properties of the cytokine interleukin-6","volume":"1813","author":"Scheller","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1111\/j.1523-1755.2004.66023.x","article-title":"Impaired monocyte cytokine production in critically ill patients with acute renal failure","volume":"66","author":"Himmelfarb","year":"2004","journal-title":"Kidney Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1359-6101(02)00027-8","article-title":"IL-6 in autoimmune disease and chronic inflammatory proliferative disease","volume":"13","author":"Ishihara","year":"2002","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1097\/01.CCM.0000228919.33620.D9","article-title":"Plasma concentrations of interleukin-6, organ failure, vasopressor support, and successful coronary revascularization in predicting 30-day mortality of patients with cardiogenic shock complicating acute myocardial infarction","volume":"34","author":"Geppert","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1681\/ASN.2003090757","article-title":"Maladaptive role of IL-6 in ischemic acute renal failure","volume":"16","author":"Kielar","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_23","first-page":"488","article-title":"Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis","volume":"23","author":"Oberholzer","year":"2005","journal-title":"Shock"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/cc8155","article-title":"Clinical review: The role of biomarkers in the diagnosis and management of community-acquired pneumonia","volume":"14","author":"Opal","year":"2010","journal-title":"Crit. Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/jmv.1045","article-title":"Symptom pathogenesis during acute influenza: Interleukin-6 and other cytokine responses","volume":"64","author":"Kaiser","year":"2001","journal-title":"J. Med. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kuller, L.H., Tracy, R., Belloso, W., De Wit, S., Drummond, F., Lane, H.C., Ledergerber, B., Lundgren, J., Neuhaus, J., and Nixon, D. (2008). Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050203"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Angulo, J., Martinez-Valdebenito, C., Marco, C., Galeno, H., Villagra, E., Vera, L., Lagos, N., Becerra, N., Mora, J., and Bermudez, A. (2017). Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005757"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Korva, M., Rus, K.R., Pavletic, M., Saksida, A., Knap, N., Jelovsek, M., Smrdel, K.S., Jakupi, X., Humolli, I., and Dedushaj, J. (2019). Characterization of Biomarker Levels in Crimean-Congo Hemorrhagic Fever and Hantavirus Fever with Renal Syndrome. Viruses, 11.","DOI":"10.3390\/v11080686"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.micinf.2008.06.006","article-title":"Role of mixed Th1 and Th2 serum cytokines on pathogenesis and prognosis of hantavirus pulmonary syndrome","volume":"10","author":"Borges","year":"2008","journal-title":"Microbes Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1006\/jsre.2002.6415","article-title":"Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway","volume":"104","author":"Desai","year":"2002","journal-title":"J. Surg. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sadeghi, M., Eckerle, I., Daniel, V., Burkhardt, U., Opelz, G., and Schnitzler, P. (2011). Cytokine expression during early and late phase of acute Puumala hantavirus infection. BMC Immunol., 12.","DOI":"10.1186\/1471-2172-12-65"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/infdis\/173.1.38","article-title":"Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome","volume":"173","author":"Linderholm","year":"1996","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Outinen, T.K., M\u00e4kel\u00e4, S.M., Ala-Houhala, I.O., Huhtala, H.S., Hurme, M., Paakkala, A.S., P\u00f6rsti, I.H., Syrj\u00e4nen, J.T., and Mustonen, J.T. (2010). The severity of Puumala hantavirus induced nephropathia epidemica can be better evaluated using plasma interleukin-6 than C-reactive protein determinations. BMC Infect. Dis., 10.","DOI":"10.1186\/1471-2334-10-132"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1086\/315522","article-title":"Systemic inflammation in hemorrhagic fever with renal syndrome correlates with hypotension and thrombocytopenia but not with renal injury","volume":"181","author":"Takala","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1053\/j.ajkd.2003.12.044","article-title":"Urinary excretion of interleukin-6 correlates with proteinuria in acute Puumala hantavirus-induced nephritis","volume":"43","author":"Mustonen","year":"2004","journal-title":"Am. J. Kidney Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1084\/jem.73.2.173","article-title":"The Occurrence during Acute Infections of a Protein Not Normally Present in the Blood: I. Distribution of the Reactive Protein in Patients\u2019 Sera and the Effect of Calcium on the Flocculation Reaction with C Polysaccharide of Pneumococcus","volume":"73","author":"Abernethy","year":"1941","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0161-5890(01)00042-6","article-title":"Human C-reactive protein: Expression, structure, and function","volume":"38","author":"Volanakis","year":"2001","journal-title":"Mol. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/S0953-6205(02)00132-2","article-title":"C-reactive protein: History and revival","volume":"13","author":"Ablij","year":"2002","journal-title":"Eur. J. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jinf.2012.08.004","article-title":"Combination of biomarkers for the discrimination between bacterial and viral lower respiratory tract infections","volume":"65","author":"Tromp","year":"2012","journal-title":"J. Infect."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Slaats, J., Ten Oever, J., van de Veerdonk, F.L., and Netea, M.G. (2016). IL-1beta\/IL-6\/CRP and IL-18\/ferritin: Distinct Inflammatory Programs in Infections. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005973"},{"key":"ref_41","first-page":"221","article-title":"C-reactive protein (CRP) and autoimmune disease: Facts and conjectures","volume":"11","author":"Szalai","year":"2004","journal-title":"Clin. Dev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/nature07468","article-title":"Structural recognition and functional activation of FcgammaR by innate pentraxins","volume":"456","author":"Lu","year":"2008","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sadeghi, M., Lahdou, I., Ettinger, J., Navid, M.H., Daniel, V., Zeier, M., Hofmann, J., Opelz, G., and Schnitzler, P. (2015). Association of low serum TGF-beta level in hantavirus infected patients with severe disease. BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0085-0"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"378","DOI":"10.3389\/fimmu.2012.00378","article-title":"Host-protective effect of circulating pentraxin 3 (PTX3) and complex formation with neutrophil extracellular traps","volume":"3","author":"Daigo","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/ni.1854","article-title":"Regulation of leukocyte recruitment by the long pentraxin PTX3","volume":"11","author":"Deban","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-065X.2008.00719.x","article-title":"The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: Interplay with cellular innate immunity","volume":"227","author":"Bottazzi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8433","DOI":"10.4049\/jimmunol.181.12.8433","article-title":"Binding of the long pentraxin PTX3 to factor H: Interacting domains and function in the regulation of complement activation","volume":"181","author":"Deban","year":"2008","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1182\/blood-2006-03-009266","article-title":"Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation","volume":"108","author":"Bozza","year":"2006","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.4049\/jimmunol.180.5.3391","article-title":"Antiviral activity of the long chain pentraxin PTX3 against influenza viruses","volume":"180","author":"Reading","year":"2008","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1161\/CIRCULATIONAHA.108.806547","article-title":"Deficiency of the long pentraxin PTX3 promotes vascular inflammation and atherosclerosis","volume":"120","author":"Norata","year":"2009","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/labinvest.2012.92","article-title":"Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice","volume":"92","author":"Han","year":"2012","journal-title":"Lab. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1161\/CIRCULATIONAHA.107.749234","article-title":"Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction","volume":"117","author":"Salio","year":"2008","journal-title":"Circulation"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Du, H., Hu, H., Wang, P., Wang, X., Zhang, Y., Jiang, H., Li, J., Bai, X., and Lian, J. (2021). Predictive value of pentraxin-3 on disease severity and mortality risk in patients with hemorrhagic fever with renal syndrome. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06145-0"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s10096-011-1392-x","article-title":"High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala hantavirus-induced nephropathia epidemica","volume":"31","author":"Outinen","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3109\/07853890.2011.573500","article-title":"Complement activation in Puumala hantavirus infection correlates with disease severity","volume":"44","author":"Sane","year":"2012","journal-title":"Ann. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1097\/MBC.0000000000000117","article-title":"Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia","volume":"25","author":"Laine","year":"2014","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Koskela, S., Makela, S., Strandin, T., Vaheri, A., Outinen, T., Joutsi-Korhonen, L., Porsti, I., Mustonen, J., and Laine, O. (2021). Coagulopathy in Acute Puumala Hantavirus Infection. Viruses, 13.","DOI":"10.3390\/v13081553"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri1457","article-title":"IDO expression by dendritic cells: Tolerance and tryptophan catabolism","volume":"4","author":"Mellor","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"F801","DOI":"10.1152\/ajprenal.00044.2007","article-title":"Proapoptotic activity of indoleamine 2,3-dioxygenase expressed in renal tubular epithelial cells","volume":"293","author":"Mohib","year":"2007","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bbrc.2005.08.232","article-title":"Indoleamine 2,3 dioxygenase and regulation of T cell immunity","volume":"338","author":"Mellor","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.it.2012.10.001","article-title":"Indoleamine 2,3 dioxygenase and metabolic control of immune responses","volume":"34","author":"Munn","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"ftw114","DOI":"10.1093\/femspd\/ftw114","article-title":"Indoleamine 2,3-dioxygenase activity is associated with regulatory T cell response in acute Puumala hantavirus infection","volume":"75","author":"Koivula","year":"2017","journal-title":"Pathog. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/jmv.22018","article-title":"High activity of indoleamine 2,3-dioxygenase is associated with renal insufficiency in Puumala hantavirus induced nephropathia epidemica","volume":"83","author":"Outinen","year":"2011","journal-title":"J. Med. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"24","DOI":"10.11613\/BM.2012.004","article-title":"Free DNA\u2014New potential analyte in clinical laboratory diagnostics?","volume":"22","author":"Wagner","year":"2012","journal-title":"Biochem. Med."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Huttunen, R., Kuparinen, T., Jylh\u00e4v\u00e4, J., Aittoniemi, J., Vuento, R., Huhtala, H., Laine, J., Syrj\u00e4nen, J., and Hurme, M. (2011). Fatal outcome in bacteremia is characterized by high plasma cell free DNA concentration and apoptotic DNA fragmentation: A prospective cohort study. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021700"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.3390\/v6072723","article-title":"Increased plasma cell-free DNA level during HTNV infection: Correlation with disease severity and virus load","volume":"6","author":"Yi","year":"2014","journal-title":"Viruses"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Outinen, T.K., Kuparinen, T., Jylh\u00e4v\u00e4, J., Lepp\u00e4nen, S., Mustonen, J., M\u00e4kel\u00e4, S., P\u00f6rsti, I., Syrj\u00e4nen, J., Vaheri, A., and Hurme, M. (2012). Plasma cell-free DNA levels are elevated in acute Puumala hantavirus infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031455"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0955-0674(00)00140-X","article-title":"Urokinase receptor and integrin partnership: Coordination of signaling for cell adhesion, migration and growth","volume":"12","author":"Ossowski","year":"2000","journal-title":"Curr. Opin. Cell. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1155\/2009\/504294","article-title":"suPAR: The molecular crystal ball","volume":"27","author":"Thuno","year":"2009","journal-title":"Dis. Markers"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1046\/j.1523-1755.2001.00719.x","article-title":"Release of urokinase plasminogen activator receptor during urosepsis and endotoxemia","volume":"59","author":"Florquin","year":"2001","journal-title":"Kidney Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1365-2796.2011.02363.x","article-title":"Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: A prospective cohort study","volume":"270","author":"Huttunen","year":"2011","journal-title":"J. Intern. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1182\/blood.V96.13.4091","article-title":"Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection","volume":"96","author":"Sidenius","year":"2000","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1365-2796.2010.02252.x","article-title":"Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population","volume":"268","author":"Andersen","year":"2010","journal-title":"J. Intern. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nm.2411","article-title":"Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis","volume":"17","author":"Wei","year":"2011","journal-title":"Nat. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"13647","DOI":"10.1038\/srep13647","article-title":"Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes","volume":"5","author":"Alfano","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Outinen, T.K., Tervo, L., M\u00e4kel\u00e4, S., Huttunen, R., M\u00e4enp\u00e4\u00e4, N., Huhtala, H., Vaheri, A., Mustonen, J., and Aittoniemi, J. (2013). Plasma levels of soluble urokinase-type plasminogen activator receptor associate with the clinical severity of acute Puumala hantavirus infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071335"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"19117","DOI":"10.1038\/s41598-020-76050-0","article-title":"Glomerular filtration barrier dysfunction in a self-limiting, RNA virus-induced glomerulopathy resembles findings in idiopathic nephrotic syndromes","volume":"10","author":"Nusshag","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/joim.12257","article-title":"Urine soluble urokinase-type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection","volume":"276","author":"Outinen","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2147\/ITT.S73223","article-title":"The role of adipokines in chronic inflammation","volume":"5","author":"Mancuso","year":"2016","journal-title":"Immunotargets Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/j.1476-5381.2011.01369.x","article-title":"Resistin: Functional roles and therapeutic considerations for cardiovascular disease","volume":"165","author":"Jamaluddin","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jcrc.2012.04.007","article-title":"Serial changes in adiponectin and resistin in critically ill patients with sepsis: Associations with sepsis phase, severity, and circulating cytokine levels","volume":"27","author":"Vassiliadi","year":"2012","journal-title":"J. Crit. Care"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Liu, K.T., Liu, Y.H., Lin, C.Y., Tsai, M.J., Hsu, Y.L., Yen, M.C., and Kuo, P.L. (2016). Serum neutrophil gelatinase-associated lipocalin and resistin are associated with dengue infection in adults. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1759-9"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e492","DOI":"10.1097\/CCM.0000000000001472","article-title":"Reversal of Acute Kidney Injury-Induced Neutrophil Dysfunction: A Critical Role for Resistin","volume":"44","author":"Singbartl","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.clim.2009.07.013","article-title":"The role of resistin as a regulator of inflammation: Implications for various human pathologies","volume":"133","author":"Filkova","year":"2009","journal-title":"Clin. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3904\/kjim.2016.229","article-title":"Linking resistin, inflammation, and cardiometabolic diseases","volume":"32","author":"Park","year":"2017","journal-title":"Korean J. Intern. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/jmv.24021","article-title":"Importance of serum adipokine and ghrelin levels in patients with Crimean-Congo hemorrhagic fever","volume":"87","author":"Yilmaz","year":"2015","journal-title":"J. Med. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Mantula, P.S., Outinen, T.K., Jaatinen, P., H\u00e4m\u00e4l\u00e4inen, M., Huhtala, H., P\u00f6rsti, I.H., Vaheri, A., Mustonen, J.T., and M\u00e4kel\u00e4, S.M. (2018). High plasma resistin associates with severe acute kidney injury in Puumala hantavirus infection. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208017"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.imbio.2018.07.020","article-title":"YKL-40: A biomarker for early nephropathy in type 2 diabetic patients and its association with inflammatory cytokines","volume":"223","author":"Umapathy","year":"2018","journal-title":"Immunobiology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1475-2840-8-61","article-title":"YKL-40\u2014An emerging biomarker in cardiovascular disease and diabetes","volume":"8","author":"Rathcke","year":"2009","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.ekir.2020.12.025","article-title":"The Associations of Plasma Biomarkers of Inflammation with Histopathologic Lesions, Kidney Disease Progression, and Mortality-The Boston Kidney Biopsy Cohort Study","volume":"6","author":"Srivastava","year":"2021","journal-title":"Kidney Int. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1080\/00365540110080233","article-title":"Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease","volume":"34","author":"Kronborg","year":"2002","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"22817","DOI":"10.3390\/ijms141122817","article-title":"Usefulness of plasma YKL-40 in management of community-acquired pneumonia severity in patients","volume":"14","author":"Wang","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.imbio.2013.04.010","article-title":"Plasma YKL-40 and CHI3L1 in systemic inflammation and sepsis-experience from two prospective cohorts","volume":"218","author":"Kornblit","year":"2013","journal-title":"Immunobiology"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Outinen, T.K., Mantula, P., Jaatinen, P., H\u00e4m\u00e4l\u00e4inen, M., Moilanen, E., Vaheri, A., Huhtala, H., M\u00e4kel\u00e4, S., and Mustonen, J. (2019). Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection. Viruses, 11.","DOI":"10.3390\/v11090767"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1002\/JLB.3VMR0118-036R","article-title":"Galectin-3-binding protein: A multitask glycoprotein with innate immunity functions in viral and bacterial infections","volume":"104","author":"Loimaranta","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Liu, K.T., Liu, Y.H., Chen, Y.H., Lin, C.Y., Huang, C.H., Yen, M.C., and Kuo, P.L. (2016). Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060832"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1093\/infdis\/164.4.819","article-title":"Lipoprotein 90K in human immunodeficiency virus-infected patients: A further serologic marker of progression","volume":"164","author":"Iacobelli","year":"1991","journal-title":"J. Infect. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1177\/0961203316644334","article-title":"Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus","volume":"25","author":"Rasmussen","year":"2016","journal-title":"Lupus"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1515\/CCLM.2000.029","article-title":"Serum protein 90K\/Mac-2BP is an independent predictor of disease severity during hepatitis C virus infection","volume":"38","author":"Kittl","year":"2000","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1099\/vir.0.066837-0","article-title":"Acute hantavirus infection induces galectin-3-binding protein","volume":"95","author":"Hepojoki","year":"2014","journal-title":"J. Gen. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1600-065X.2010.00954.x","article-title":"From the cradle to the grave: Activities of GATA-3 throughout T-cell development and differentiation","volume":"238","author":"Hosoya","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5223","DOI":"10.1182\/blood-2007-10-115857","article-title":"Repression via the GATA box is essential for tissue-specific erythropoietin gene expression","volume":"111","author":"Obara","year":"2008","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"608","DOI":"10.5414\/CNP71608","article-title":"GATA-3 is upregulated in peripheral blood mononuclear cells from patients with minimal change nephrotic syndrome","volume":"71","author":"Komatsuda","year":"2009","journal-title":"Clin. Nephrol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Libraty, D.H., M\u00e4kel\u00e4, S., Vlk, J., Hurme, M., Vaheri, A., Ennis, F.A., and Mustonen, J. (2012). The Degree of Leukocytosis and Urine GATA-3 mRNA Levels Are Risk Factors for Severe Acute Kidney Injury in Puumala Virus Nephropathia Epidemica. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035402"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.2215\/CJN.00980110","article-title":"The origin of multiple molecular forms in urine of HNL\/NGAL","volume":"5","author":"Cai","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1053\/j.ajkd.2009.07.020","article-title":"Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: A systematic review and meta-analysis","volume":"54","author":"Haase","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Bunz, H., Weyrich, P., Peter, A., Baumann, D., Tschritter, O., Guthoff, M., Beck, R., Jahn, G., Artunc, F., and Haring, H.U. (2015). Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) and proteinuria predict severity of acute kidney injury in Puumala virus infection. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1180-9"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"332","DOI":"10.7150\/ijms.39367","article-title":"Procalcitonin: A promising tool or just another overhyped test?","volume":"17","author":"Paudel","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000368479","article-title":"Determination of procalcitonin levels in patients with nephropathia epidemica\u2014A useful tool or an unnecessary diagnostic procedure?","volume":"40","author":"Latus","year":"2015","journal-title":"Kidney Blood Press Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1080\/23744235.2017.1358461","article-title":"Haematuria is a marker for the severity of acute kidney injury but does not associate with thrombocytopenia in acute Puumala hantavirus infection","volume":"49","author":"Outinen","year":"2017","journal-title":"Infect. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000459634","article-title":"Glomerular proteinuria predicts the severity of acute kidney injury in Puumala hantavirus induced tubulointerstitial nephritis","volume":"136","author":"Mantula","year":"2017","journal-title":"Nephron"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.ekir.2019.05.770","article-title":"Glucosuria predicts the severity of Puumala hantavirus infection","volume":"4","author":"Mantula","year":"2019","journal-title":"Kidney Int. Rep."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/1\/45\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:54:50Z","timestamp":1760169290000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/1\/45"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,28]]},"references-count":112,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["v14010045"],"URL":"https:\/\/doi.org\/10.3390\/v14010045","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,28]]}}}