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What is suPAR?

suPAR (soluble urokinase plasminogen activating receptor) is a protein in the blood.
The plasma level of suPAR reflects immune activation and is increased in several infectious diseases, such as HIV-1-infection, malaria, tuberculosis, Streptococcus pneumonia bacteraemia, sepsis, pneumococcal pneumonia and bacterial and viral CNS infection [1-11]. Furthermore, high suPAR levels are associated with increased inflammation, disease progression and risk of mortality. Measuring suPAR levels can thus serve as a marker to determine chances for survival upon hospital admission as well as for monitoring for prevention of disease progression and earlier intervention time point.

The suPAR protein
suPAR is the soluble form of the urokinase-type plasminogen activator receptor (uPAR), a three domain receptor [12] mainly expressed on immune cells, including neutrophils, activated T-cells, and macrophages.

whatissupar

Figure 1. Schematic representation of urokinase receptor The GPI-anchor links uPAR to the cell membrane making it available for uPA to bind to the receptor (1 A). When the receptor is cleaved between the GPI-anchor and D3, it becomes soluble (suPAR) (1 B). suPAR is a stable protein that can be measured in various body fluids. uPA: urokinase-type plasminogen activator, uPAR: uPA receptor, suPAR: soluble uPAR, 1: Domain 1, D2: Domain 2, D3: Domain 3

The membrane-bound uPAR is illustrated in figure 1 A. uPAR is linked to the cell membrane by a glycosyl phosphatidylinositol (GPI)-anchor and binding of urokinase plasminogen activator (uPA) to uPAR, facilitates cleavage of the anchor and hence shedding of the receptor (Fig 1.)[12]. Once this anchor is cleaved the protein is released from the membrane and becomes soluble as illustrated in figure 1 B.

Biological Function
uPAR and its ligand are involved in numerous physiological and pathological pathways, which include the plasminogen activating pathway, regulation of pericellular proteolysis, modulation of cell adhesion, migration and proliferation through interactions with proteins present in the extracellular matrix[13]. The involvement of the soluble form of the receptor in the inflammation process is well documented although the actual biological function of the molecule is still not clear. Studies suggest that suPAR is a regulator of uPAR/uPA actions through competitive inhibition of uPAR and several studies conclude that the cleaved receptor is a chemotatic agent promoting the immune response [12].

1: Langkilde A et al., Inflammation in HIV-infected patients: impact of HIV, lifestyle, body composition, and demography - a cross sectional cohort study, PLoS One. 2012;7(12).
2: Oliviera I et al., Assessment of simple risk markers for early mortality among HIV-infected patients in Guinea-Bissau: a cohort study BMJ Open. 2012 Nov 14;2(6).
3: Wittenhagen et al., The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniaebacteraemia and predicts mortality, Clin Microbiol Infect. 2004 May;10(5):409-15.
4: Tzanakaki G, et al., Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome, Eur J Clin Microbiol Infect Dis. 2012 Jun;31(6):1157-62.
5: Ostergaard C et al., Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome, Scand J Infect Dis. 2004;36(1):14-9.
6: Yilmaz et al. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in systemic inflammatory response syndrome, Clin Biochem. 2011 Oct;44(14-15):1227-30.
7: Uusitalo-Seppälä R et al., Soluble urokinase-type plasminogen activator receptor in patients with suspected infection in the emergency room: a prospective cohort study, J Intern Med. 2012 Sep;272(3):247-56.
8: Koch A & Tacke F, Why high suPAR is not super--diagnostic, prognostic and potential pathogenic properties of a novel biomarker in the ICU, Crit Care. 2011;15(6):1020.
9: Ostrowski SR, Elevated plasma urokinase receptor predicts low birth weight in maternal malaria, Parasite Immunol. 2007 Jan;29(1):37-46.
10: Mardining Rasas TY et al., Soluble urokinase plasminogen activator receptor levels in tuberculosis patients at high risk for multidrug resistance. Tuberc Res Treat. 2012;2012:240132.
11: Rabna P et al., Utility of the plasma level of suPAR in monitoring risk of mortality during TB treatment, PLoS One. 2012;7(8):e43933.
12: Huai Q, et al. Structure of human urokinase plasminogen activator in complex with its receptor, Science. 2006 Feb 3;311(5761):656-9.
13: Thunø M et al., suPAR: the molecular crystal ball, Dis Markers. 2009;27(3):157-72.

For information about how to measure suPAR, please look under suPARnostic Products.

For more scientific information about suPAR, please read here:

arrow icon suPAR as a marker for Immune Activation
arrow icon Key Publications

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