Plasma levels of soluble urokinase-type plasminogen activator receptor associate with the clinical severity of acute Puumala hantavirus infection

PLoS One. 2013 Aug 21;8(8):e71335. doi: 10.1371/journal.pone.0071335. eCollection 2013.

Abstract

Objectives: 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.

Design: A single-centre prospective cohort study.

Subjects and methods: 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).

Results: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation*
  • Hemorrhagic Fever with Renal Syndrome / blood*
  • Hemorrhagic Fever with Renal Syndrome / diagnosis*
  • Humans
  • Inflammation
  • Male
  • Middle Aged
  • Prospective Studies
  • Puumala virus
  • Receptors, Urokinase Plasminogen Activator / blood*
  • Young Adult

Substances

  • Receptors, Urokinase Plasminogen Activator

Grants and funding

This study was financially supported by the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (9P031, Fimlab X50000), European Commission Project “Diagnosis and control of rodent-borne viral zoonoses in Europe” (QLK2-CT-2002-01358), and by grants from the Sigrid Jusélius Foundation, the Finnish Kidney Foundation and the Orion-Farmos Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.