Association of soluble urokinase plasminogen activator receptor levels with fibrotic and vascular manifestations in systemic sclerosis

PLoS One. 2021 Feb 22;16(2):e0247256. doi: 10.1371/journal.pone.0247256. eCollection 2021.

Abstract

Objective: We assessed the association of suPAR (soluble urokinase plasminogen activator receptor) plasma levels with fibrotic and vascular manifestations in patients with systemic sclerosis (SSc).

Methods: suPAR plasma levels were measured in 121 consecutive patients with SSc and correlated to pulmonary and vascular features of SSc, including interstitial lung disease as characterized by percentage of predicted CO diffusing capacity (DLco) and forced vital capacity (FVC), pulmonary fibrosis by computed tomography, and pulmonary arterial hypertension, telangiectasias, and digital ulcers.

Results: Overall, 121 SSc patients (84% females; mean age, 57 ± 12 [range: 22-79] years) were enrolled; 35% had diffuse cutaneous SSc. suPAR plasma levels ranged from 1.3-10.2 [median: 2.9 (p25-p75: 2.3-3.9)] ng/mL. Log(suPAR) levels correlated with DLco (r = -0.41, p <0.0001) and FVC (r = -0.26, p = 0.004), also when adjusted for age, sex, and pulmonary hypertension. A suPAR cut-off level of >2.5 ng/mL showed a sensitivity of 91% for identifying patients with either DLco <50% or FVC < 60% of the predicted values. Similarly, 19 (90%) had a suPAR >2.5 ng/mL among those diagnosed with pulmonary fibrosis vs. 59 (60%) among those who did not (p = 0.008). suPAR values were not associated with vascular manifestations.

Conclusion: suPAR levels strongly correlated with pulmonary involvement in SSc. Future studies should test if suPAR estimation can be used for surveillance of severe pulmonary involvement in SSc.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Fibrosis / metabolism*
  • Humans
  • Hypertension, Pulmonary / metabolism
  • Lung / metabolism*
  • Male
  • Middle Aged
  • Receptors, Urokinase Plasminogen Activator / metabolism*
  • Respiratory Function Tests / methods
  • Scleroderma, Systemic / metabolism*
  • Vital Capacity / physiology
  • Young Adult

Substances

  • Receptors, Urokinase Plasminogen Activator

Grants and funding

The authors received no specific funding for this work.