Plasma Levels of Soluble Urokinase-Type Plasminogen Activator Receptor Associate with the Clinical Severity of Acute Puumala Hantavirus Infection

• Published in: PloS one Vol. 8; no. 8; p. e71335
• Main Authors: Outinen, Tuula K., Tervo, Laura, Mäkelä, Satu, Huttunen, Reetta, Mäenpää, Niina, Huhtala, Heini, Vaheri, Antti, Mustonen, Jukka, Aittoniemi, Janne
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.08.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Blood; Convalescence; Correlation; Creatinine; Cytokines; Deoxyribonucleic acid; DNA; Enzyme-Linked Immunosorbent Assay; Family medical history; Female; Fever; Gene Expression Regulation; Glycoproteins; Hantavirus; Health aspects; Hematocrit; Hemorrhagic Fever with Renal Syndrome - blood; Hemorrhagic Fever with Renal Syndrome - diagnosis; Hepatitis; HIV; Hospitals; Human immunodeficiency virus; Humans; Infection; Infections; Inflammation; Integrins; Internal medicine; Laboratories; Leukocytes; Male; Medicine; Middle Aged; Mortality; Pathogenesis; Patients; Plasma levels; Prospective Studies; Puumala virus; Receptors, Urokinase Plasminogen Activator - blood; Thrombolytic drugs; U-Plasminogen activator; Urokinase; Young Adult; Finland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0071335

Urokinase-type plasminogen activator receptor is a multifunctional glycoprotein, the expression of which is increased during inflammation. It is known to bind to β3-integrins, which are elementary for the cellular entry of hantaviruses. Plasma soluble form of the receptor (suPAR) levels were evaluated as a predictor of severe Puumala hantavirus (PUUV) infection and as a possible factor involved in the pathogenesis of the disease. A single-centre prospective cohort study. Plasma suPAR levels were measured twice during the acute phase and once during the convalescence in 97 patients with serologically confirmed acute PUUV infection using a commercial enzyme-linked immunosorbent assay (ELISA). The plasma suPAR levels were significantly higher during the acute phase compared to the control values after the hospitalization (median 8.7 ng/ml, range 4.0-18.2 ng/ml vs. median 4.7 ng/ml, range 2.4-12.2 ng/ml, P<0.001). The maximum suPAR levels correlated with several variables reflecting the severity of the disease. There was a positive correlation with maximum leukocyte count (r = 0.475, p<0.001), maximum plasma creatinine concentration (r = 0.378, p<0.001), change in weight during the hospitalization (r = 0.406, p<0.001) and the length of hospitalization (r = 0.325, p = 0.001), and an inverse correlation with minimum platelet count (r = -0.325, p = 0.001) and minimum hematocrit (r = -0.369, p<0.001). Plasma suPAR values are markedly increased during acute PUUV infection and associate with the severity of the disease. The overexpression of suPAR possibly activates β3-integrin in PUUV infection, and thus might be involved in the pathogenesis of the disease.