suPAR in Clinical Settings
Interestingly, in all of these conditions the higher the concentration of suPAR, the worse the prognosis of the disease[Sier et al., 1998; Slot et al., 1999; Stephens et al., 1999; Sidenius et al., 2000b; Balabanov et al., 2001; Eugen-Olsen et al., 2002; Perch et al., 2004; Wittenhagen et al., 2004, Østergaard et al., 2004].
Sidenius et al. first investigated the correlation between serum suPAR levels and HIV-1 disease prognosis in 2000 and found the by now well documented increase of suPAR levels in HIV-1 infected individuals and its power as a prognostic marker, with strength similar to, and independent of, CD4 counts and viral load [Sidenius et al., 2000b; Ostrowski et al., 2005b].
Hereafter the picture broadened to reveal that suPAR’s predictive power is unspecific to the respective disease, as it reflects the overall systemic inflammation and immune activation common to many life-threatening diseases. In agreement with the hypothesis of immune activation/inflammation, a high level of suPAR was associated with worse prognosis in several diseases, including tuberculosis [reviewed by Djoba Siawaya et al, 2007] and malaria [Ostrowski et al, 2005a].
For clinical practice, the fact that plasma suPAR levels are not affected by uPAR promoter polymorphisms [Schneider et al., 2007] increase the potential value of suPAR as a biomarker for HIV progression and treatment initiation. Also in patients receiving HAART, suPAR was shown to decrease with effective therapy suggesting its potential as a treatment efficacy marker [Ostrowski et al., 2004] with potential clinical benefits.
Overall, the above described studies argue for a place of suPAR amongst routine patient assessment. The greatest value of suPARnostic® in tuberculosis management is its monitoring value, as doctors can follow treatment responses. In HIV settings, the general practise is dominated by HIV RNA viral load and CD4 cell counts, the former of which requires expensive, high technology laboratory facilities.
suPAR is proposed as a robust and reliable prognostic marker that can also be used in resource-limited settings. Latest, suPAR was shown to be a potential standardized assessment tool in critical care [Kofoed et al., 2006]. This is of clear importance as economic as well as patient survival considerations are calling for better tools to evaluate the state of patients with community-acquired infections, most notably with the systemic inflammatory response syndrome (SIRS).
