Home Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis
Article
Licensed
Unlicensed Requires Authentication

Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis

  • Nóra Legány , Gergely Toldi , Jörg H.W. Distler , Christian Beyer , Balázs Szalay , László Kovács , Barna Vásárhelyi and Attila Balog EMAIL logo
Published/Copyright: April 18, 2015

Abstract

Background: Urokinase plasminogen activator receptor (uPAR) is a key component of the fibrinolytic system involved in extracellular matrix remodeling and angiogenesis. Novel animal models supported the key role of uPAR not only in fibrosis but also in systemic sclerosis (SSc)-related microvascular abnormalities. The aim of this study was to investigate plasma soluble uPAR (suPAR) levels in SSc, and their association with organ-specific involvement.

Methods: suPAR concentrations were measured by ELISA in SSc patient (n=83) and in healthy controls (n=29). Simultaneously, CRP and ESR were assessed. Detailed clinical data including skin, lung, heart and microvascular characteristics were evaluated at sampling.

Results: suPAR values were higher in SSc patients than in controls. Subgroup analysis showed higher suPAR values in diffuse cutaneous- than in limited cutaneous SSc and correlated with anti-Scl-70+. suPAR levels also associated with pulmonary function test parameters of fibrosis, presence of microvascular lesions (e.g., Raynaud phenomenon, naifold capillaroscopic abnormalities and digital ulcers) and arthritis.

Conclusions: Our data indicate that suPAR might be a valuable early diagnostic marker of SSc which also correlates with disease severity.


Corresponding author: Attila Balog, MD, PhD, Faculty of Medicine, Department of Rheumatology, Albert Szent-Györgyi Health Center, University of Szeged, Kálvária sgt. 57, 6725, Szeged, Hungary, Phone/Fax: +36 62561332, E-mail:

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. Study conception and design: NL, AB; Data collection and analysis, review and approve the final manuscript: NL, AB, GT, LK, JD, CB, BSz, BV; Analysis and interpretation of data: NL, AB, GT, LK, JD, VB;NL, JD, BV, AB wrote the manuscript.

Financial support: The study was supported by Hungarian Scientific Research Fund (OTKA) (Grant no. 101661) and by the research grant of Hungarian Association of Rheumatologist (2014). Attila Balog and Gergely Toldi was supported by the Zoltán Magyary Scholarship (grant no. TÁMOP-4.2.4. A/2-11-1-2012-001).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 2007;117:557–67.10.1172/JCI31139Search in Google Scholar PubMed PubMed Central

2. Muangchan C, Pope J. The significance of interleukin-6 and C-reactive protein in systemic sclerosis: a systematic literature review. Clin Exp Rheumatol 2013;31:122–34.Search in Google Scholar

3. Manetti M, Guiducci S, Romano E, Avouac J, Rosa I, Ruiz B, et al. Decreased expression of the endothelial cell-derived factor EGFL7 in systemic sclerosis: potential contribution to impaired angiogenesis and vasculogenesis. Arthritis Res Ther 2013;15:R165.10.1186/ar4349Search in Google Scholar PubMed PubMed Central

4. Manetti M, Guiducci S, Romano E, Bellando-Randone S, Conforti ML, Ibba-Manneschi L, et al. Increased serum levels and tissue expression of matrix metalloproteinase-12 in patients with systemic sclerosis: correlation with severity of skin and pulmonary fibrosis and vascular damage. Ann Rheum Dis 2012;71:1064–72.10.1136/annrheumdis-2011-200837Search in Google Scholar PubMed

5. Mondino A, Resnati M, Blasi F. Structure and function of the urokinase receptor. Thromb Haemost 1999;82:19–22.10.1055/s-0037-1615547Search in Google Scholar

6. Balsara RD, Merryman R, Virjee F, Northway C, Castellino FJ, Ploplis VA. A deficiency of uPAR alters endothelial angiogenic function and cell morphology. Vasc Cell 2011;3:10.10.1186/2045-824X-3-10Search in Google Scholar PubMed PubMed Central

7. Margheri F, Manetti M, Serrati S, Nosi D, Pucci M, Matucci-Cerinic M, et al. Domain 1 of the urokinase-type plasminogen activator receptor is required for its morphologic and functional, β2 integrin-mediated connection with actin cytoskeleton in human microvascular endothelial cells: failure of association in systemic sclerosis endothelial cells. Arthritis Rheum 2006;54:3926–38.10.1002/art.22263Search in Google Scholar PubMed

8. Kanno Y, Kaneiwa A, Minamida M, Kanno M, Tomogane K, Takeuchi K, et al. The absence of uPAR is associated with the progression of dermal fibrosis. J Invest Dermatol 2008;128:2792–7.10.1038/jid.2008.157Search in Google Scholar PubMed

9. Bernstein AM, Twining SS, Warejcka DJ, Tall E, Masur SK. Urokinase receptor cleavage: a crucial step in fibroblast-to-myofibroblast differentiation. Mol Biol Cell 2007;18:2716–27.10.1091/mbc.e06-10-0912Search in Google Scholar PubMed PubMed Central

10. Toldi G, Bekö G, Kádár G, Mácsai E, Kovács L, Vásárhelyi B, et al. Soluble urokinase plasminogen activator receptor (suPAR) in the assessment of inflammatory activity of rheumatoid arthritis patients in remission. Clin Chem Lab Med 2013;51:327–32.10.1515/cclm-2012-0221Search in Google Scholar PubMed

11. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737–47.10.1002/art.38098Search in Google Scholar PubMed PubMed Central

12. LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988;15:202–5.Search in Google Scholar

13. Manetti M, Rosa I, Milia AF, Guiducci S, Carmeliet P, Ibba-Manneschi L, et al. Inactivation of urokinase-type plasminogen activator receptor (uPAR) gene induces dermal and pulmonary fibrosis and peripheral microvasculopathy in mice: a new model of experimental scleroderma? Ann Rheum Dis 2014;73:1700–9.10.1136/annrheumdis-2013-203706Search in Google Scholar PubMed

14. Manetti M, Allanore Y, Revillod L, Fatini C, Guiducci S, Cuomo G, et al. A genetic variation located in the promoter region of the UPAR (CD87) gene is associated with the vascular complications of systemic sclerosis. Arthritis Rheum 2011;63:247–56.10.1002/art.30101Search in Google Scholar PubMed

15. Balabanov R, Lisak D, Beaumont T, Lisak RP, Dore-Duffy P. Expression of urokinase plasminogen activator receptor on monocytes from patients with relapsing-remitting multiple sclerosis: effect of glatiramer acetate (copolymer 1). Clin Diagn Lab Immunol 2001;8:1196–203.10.1128/CDLI.8.6.1196-1203.2001Search in Google Scholar PubMed PubMed Central

16. Riisbro R, Christensen IJ, Høgdall C, Brünner N, Høgdall E. Soluble urokinase plasminogen activator receptor measurements: infuence of sample handling. Int J Biol Markers 2001;16:233–9.10.1177/172460080101600402Search in Google Scholar

17. Bandinelli F, Bartoli F, Perfetto E, Del Rosso A, Moggi-Pignone A, Guiducci S, et al. The fibrinolytic system components are increased in systemic sclerosis and modulated by Alprostadil (alpha1 ciclodestryn). Clin Exp Rheumatol 2005;23:671–7.Search in Google Scholar

18. Smith V, Decuman S, Sulli A, Bonroy C, Piettte Y, Deschepper E, et al. Do worsening scleroderma capillaroscopic patterns predict future severe organ involvement? A pilot study. Ann Rheum Dis 2012;71:1636–9.10.1136/annrheumdis-2011-200780Search in Google Scholar PubMed

Received: 2015-1-22
Accepted: 2015-3-5
Published Online: 2015-4-18
Published in Print: 2015-10-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Laboratory medicine does matter in science (and medicine)… yet many seem to ignore it
  4. The standardization of the urine albumin assays: no longer deferrable
  5. Reviews
  6. The role of telomeres and vitamin D in cellular aging and age-related diseases
  7. Atypical hemolytic uremic syndrome: from diagnosis to treatment
  8. Clinical relevance and contemporary methods for counting blood cells in body fluids suspected of inflammatory disease
  9. EFLM Opinion Paper
  10. How to assess the quality of your analytical method?
  11. Genetics and Molecular Diagnostics
  12. Validation of CFTR intronic variants identified during cystic fibrosis population screening by a minigene splicing assay
  13. General Clinical Chemistry and Laboratory Medicine
  14. Uncertainty in measurement for 43 biochemistry, immunoassay, and hemostasis routine analytes evaluated by a method using only external quality assessment data
  15. A study examining the bias of albumin and albumin/creatinine ratio measurements in urine
  16. National survey on appropriateness of clinical biochemistry reporting in China
  17. Potentiometric measurement of urinary iodine concentration in patients with thyroid diseases with and without previous exposure to non-radioactive iodine
  18. Determination of 21-hydroxylase autoantibodies: inter-laboratory concordance in the Euradrenal International Serum Exchange Program
  19. Value of a commercial kit for detecting anti-C1q autoantibodies and correlation with immunological and clinical activity of lupus nephritis
  20. Comparison of the bead-based simultaneous analysis of specific platelet antibodies assay (SASPA) and Pak Lx Luminex technology with the monoclonal antibody immobilization of platelet antigens assay (MAIPA) to detect platelet alloantibodies
  21. Measurement of the inflammatory response in the early postoperative period after hip and knee arthroplasty
  22. Whole blood thromboelastometry profiles in women with preeclampsia
  23. Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis
  24. Reference Values and Biological Variations
  25. Reference ranges of serum bile acids in children and adolescents
  26. Infectious Diseases
  27. Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection
  28. Cardiovascular Diseases
  29. Head-to-head comparison of 10 natriuretic peptide assays
  30. Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors
  31. Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death
  32. Identification of molecular species of oxidized triglyceride in plasma and its distribution in lipoproteins
  33. A new formula for estimation of low-density lipoprotein cholesterol in an ethnic Chinese population
  34. Letter to the Editors
  35. Laboratory medicine: let’s say it is the mirror of science (and medicine)
  36. The economic burden of hemolysis
  37. Acute effects of conventional and extended hemodialysis and hemodiafiltration on high-sensitivity cardiac troponins
  38. Cuvette carryover with the gentamicin assay on the Beckman AU480 analyser
  39. Comparison study of two commercially available methods for the determination of golimumab and anti-golimumab antibody levels in patients with rheumatic diseases
  40. Automated alkaline-pH electrophoresis followed by densitometry does not correlate with cation-exchange (CE)-HPLC in quantification of HbA2 and variant hemoglobins
  41. Progression from light chain myeloma to secondary plasma cell leukemia accompanied by peripheral blood eosinophilia
  42. Harmonization of results has not been fully achieved for serum immunoglobulin measurements
  43. The risk of macrovascular complications in subjects genotyped for common IL-6 gene and TNF-α gene variants
  44. Comparison of nucleated red blood cell count with four commercial hematological analyzers
  45. Reply to: The risk of macrovascular complications in subjects genotyped for common IL-6 gene and TNF-α gene variants
  46. Congress Abstracts
  47. Congress of Clinical Chemistry and Laboratory Medicine
  48. 47th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
  49. 15th EFLM Continuous Postgraduate Course in Clinical Chemistry and Laboratory Medicine
Downloaded on 6.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2015-0079/html
Scroll to top button