SuPAR

suPAR, soluble urokinase-type plasminogen activator receptor (NCBI Accession no. AAK31795) is the soluble form of uPAR. uPAR is a membrane bound receptor for uPA, otherwise known as urokinase as well as Vitronectin. suPAR results from the cleavage and release of membrane-bound uPAR. suPAR concentration positively correlates to the activation level of the immune system and is present in plasma, urine, blood, serum, and cerebrospinal fluid. suPAR is a marker of disease severity and aggressiveness.[1]

Molecular characteristics

suPAR has a secondary structure of 17 anti parallel β-sheets with three short α-helices. There are three homologous domains of suPAR: DI, DII, and DIII. In the comparison of cDNA sequences, DI differs from DII and DIII in its primary and tertiary structure, causing its distinct ligand binding properties.[1][2]

The GPI-anchor links uPAR to the cell membrane making it available for uPA binding. When uPA is bound to the receptor, there is cleavage between the GPI-anchor and DIII, forming suPAR.[3] There are three different suPAR forms: suPARI-III, suPARII-III, and suPARI. Of these three forms suPARII-III is known to be a chemotactic agent for promoting the immune system.[1]

Application

suPAR is a biomarker for activation of the inflammatory and immune systems. suPAR levels are positively correlated with pro-inflammatory biomarkers, such as tumor necrosis factor-α, leukocyte counts, and C-reactive protein. It has also been associated with organ damage in various diseases.[4][5][6][7] Elevated levels of suPAR are associated with increased risk of systemic inflammatory response syndrome (SIRS), cancer, Focal segmental glomerulosclerosis, cardiovascular disease, type 2 diabetes, infectious diseases, HIV, and mortality.[8] suPARnostic is a prognostic test used to detect suPAR levels in blood plasma.

A recent study[9] predicts that High levels of the protein suPAR in the blood of a person with COVID-19 may be a predictor of a more severe disease course.

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References
  1. Thunø, Maria; Macho, Betina; Eugen-Olsen, Jesper (2009). "SuPAR: The Molecular Crystal Ball". Disease Markers. 27 (3–4): 157–72. doi:10.1155/2009/504294. PMC 3835059. PMID 19893210.
  2. M. Huang, A. P. Mazar, G. Parry, A. A.-R. “Higazi, A. Kuo and D. B. Cines. Crystallization of soluble urokinase receptor (suPAR) in complex with urokinase amino-terminal fragment (1-143)”. Acta Crystallographica (2005): D61 (6), 697-700.
  3. "What is suPAR? | Quick Links". Suparnostic.com. Retrieved 2012-05-09.
  4. Enocsson, Helena; Sjöwall, Christopher (15 April 2015). "Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?". Clinica Chimica Acta. 444: 234–241. doi:10.1016/j.cca.2015.02.031. PMID 25704300.
  5. Enocsson, Helena; Wetterö, Jonas; Skogh, Thomas; Sjöwall, Christopher (2013). "Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus". Translational Research. 162 (5): 287–296. doi:10.1016/j.trsl.2013.07.003. PMID 23916811.
  6. Sjöwall, C; Martinsson, K; Cardell, K; Ekstedt, M; Kechagias, S (2014). "Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in non-alcoholic fatty liver disease". Translational Research. 165 (6): 658–66. doi:10.1016/j.trsl.2014.09.007. PMID 25445207.
  7. Hahm, E; et al. (December 2016). "Bone marrow-derived immature myeloid cells are a main source of circulating suPAR contributing to proteinuric kidney disease". Nature Medicine. 23 (1): 100–106. doi:10.1038/nm.4242. PMC 5405698. PMID 27941791.
  8. Eugen-Olsen, J. et al. "Circulating Soluble Urokinase Plasminogen Activator Receptor Predicts Cancer, Cardiovascular Disease, Diabetes and Mortality in the General Population."Journal of Internal Medicine (2010).
  9. "Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia". Critical Care. 2020-04-30.
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