suPAR as a biomarker for pulmonary disease
The suPAR level is elevated in patients with infections and chronic diseases of the lungs and respiratory tract compared to healthy individuals, and a high suPAR level is associated with:
- Bacteremia and sepsis1-4
- Asthma and poor disease control in asthma8
- COPD and in relation to an exacerbation9,10
- Incidence of future respiratory cancer11
- Poor prognosis1-7
In general, the suPAR level reflects immune activation regardless of etiology, and therefore the suPAR level is of no diagnostic value. However, in SIRS patients it has been demonstrated that the suPAR level is able to discriminate patients with bacteremia from patients with no bacteremia. A combined model using suPAR, procalcitonin, and IL-6 showed an AUC of 0.804 for prediction of bacteremia in SIRS patients1.
The prognostic value of suPAR has been studied among patients with S. pneumoniae bacteremia2 and in patients with
S. pneumoniae, S. aureus or E. coli bacteremia3. In both situations, significantly higher suPAR values were found in non-survivors. In the bacteremia patients, a sensitivity of 83% and a specificity of 76% for mortality is found using a cut-off value of 11.0 ng/mL. A similar prognostic value is found in a study of patients with sepsis. Here, a cut-off value of 12 ng/mL is linked to a >80% sensitivity and a negative predictive value of 94.5% for mortality4. In mechanically ventilated patients5 and in children with pneumonia6,7, the suPAR level is elevated and associated with seriousness of the disease and a poorer prognosis.
The suPAR level correlates with respiratory obstruction and can potentially help with the objective assessment of asthma8. In addition, the median suPAR level is significantly higher in asthmatics compared to healthy individuals (3.3 ng/mL vs. 2.5 ng/mL)9.
Similarly, in COPD patients, the suPAR level is significantly higher compared to healthy individuals, and the median level is above the level in asthma patients (5.8 ng/mL vs. 3.3 ng/mL)9.
Serum suPAR, CRP, and fibrinogen are significantly higher in COPD patients experiencing an exacerbation compared to healthy controls (4.8 ± 1.9 ng/mL vs. 2.4 ± 0.9 ng/mL, respectively). suPAR was superior to fibrinogen and CRP in identifying COPD patients experiencing an exacerbation, and in multivariable analyses, only suPAR and fibrinogen were predictors of an exacerbation. Moreover, a negative correlation between suPAR and lung function, measured by FEV1, was found10.
In the general population, suPAR is associated with the incidence of respiratory cancer, even after adjustment for traditional risk factors, CRP, and leucocytes11.
In a study including 2838 acutely admitted medical patients with COPD as primary (AECOPD) or secondary diagnose, median suPAR levels were significantly higher among patients who died within 30 days compared with those who survived (5.7 ng/ml (IQR 3.8-8.1) vs. 3.6 ng/ml (2.7-5.1), P < 0.0001)12.
1. Hoenigl, M., Raggam, R.B., Wagner, J., Valentin, T., Leitner, E., Seeber, K., Zollner- Schwetz, I., Krammer, W., Prüller, F., Grisold, A.J., Krause, R., 2013. Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR) for prediction of bacteremia in patients with systemic inflammatory response syn- drome. Clin. Biochem. 46, 225–229.
2. Wittenhagen, P., Kronborg, G., Weis, N., Nielsen, H., Obel, N., Pedersen, S.S., Eugen- Olsen, J., 2004. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality. Clin. Microbiol. Infect. 10, 409–415.
3. Huttunen, R., Syrjanen, J., Vuento, R., Hurme, M., Huhtala, H., Laine, J., Pessi, T., Aittoniemi, J., 2011. 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. J. Intern. Med. 270, 32–40.
4. Giamarellos-Bourboulis EJ, Norrby-Teglund A, Mylona V, Savva A, Tsangaris I,Dimopoulou I, et al. Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care 2012;16:R149.
5. Savva, A., Raftogiannis, M., Baziaka, F., Routsi, C., Antonopoulou, A., Koutoukas, P., Tsaganos, T., Kotanidou, A., Apostolidou, E., Giamarellos-Bourboulis, E.J., Dimopoulos, G., 2011. Soluble urokinase plasminogen activator receptor (suPAR) for assessment of disease severity in ventilator-associated pneumonia and sepsis. J. Infect. 63, 344–350.
6. Wrotek, A., Pawlik, K., Jackowska, T., 2013. Soluble receptor for urokinase plasmino- gen activator in community-acquired pneumonia in children. Adv. Exp. Med. Biol. 788, 329–334.
7. Wrotek, A., Jackowska, T., Pawlik, K., 2015. Soluble urokinase plasminogen activator receptor: an indicator of pneumonia severity in children. Adv. Exp. Med. Biol. 835, 1–7, 2014 40
8. Ivancsó, I., Toldi, G., Bohács, A., Eszes, N., Müller, V., Rigó Jr., J., Vásárhelyi, B., Losonczy,G., Tamási, L., 2013. Relationship of circulating soluble urokinase plasminogenactivator receptor (suPAR) levels to disease control in asthma and asthmaticpregnancy. PLoS ONE 8, e60697.
9. Portelli M, Siedlinski M, Stewart C et al. Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels. FASEB J. 2014 Feb;28(2):923-34
10. Gumus A, Altintas N, Cinarka H, Kirbas A, Hazıroglu M, Karatas M, Sahin U. Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD.Int J Chron Obstruct Pulmon Dis. 2015 Feb 13;10:357-65.
11. Langkilde A, Hansen TW, Ladelund S, Linneberg A, Andersen O, Haugaard SB, Jeppesen J, Eugen-Olsen J Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals.Cancer Epidemiol Biomarkers Prev. 2011 Apr;20(4):609-18.
12. Godtfredsen NS, Jørgensen DV,, Marsaa K, Ulrik CS,, Andersen O, Eugen-Olsen J, Rasmussen LJH. Soluble urokinase plasminogen activator receptor predicts mortality in exacerbated COPD. Respir Res. 2018 21;19(1):97.