ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
This article is part of the Research TopicSystemic Sclerosis: Immunological ImpactsView all articles
Serum Profiling of uPA, PAI-1, and suPAR in Systemic Sclerosis: A Preliminary Study on Analytical Aspects and Associations with Microvascular and Fibrotic Manifestations
Provisionally accepted
Filomena Napolitano
Ilaria Mormile
Gabriele Mignogna
Amato De Paulis
Francesca Wanda Rossi*
Nunzia Montuori- Department of Translational Medical Sciences, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
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Introduction: In Systemic Sclerosis (SSc), the laboratory panel lacks biomarkers able to predict disease courses and/or reflect fibrotic activity in the skin and internal organs. We assessed the association of serum levels of urokinase (uPA), plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase plasminogen activator receptor (suPAR) with microvascular and fibrotic manifestations. Methods: A total of 21 SSc patients were enrolled in the study. Serum levels of PAI-1, uPA and suPAR were measured by ELISA and diagnostic performance of two widely debated suPAR ELISA kits, such as Human suPAR ELISA (Biovendor R&D, Brno, Czech Republic) and suPARnostic ELISA (Virogates, Copenaghen, Denmark), were examined in SSc patients and in healthy controls. Serum uPA, PAI-1 and suPAR levels were correlated to conventional fibrotic and vascular markers, such as TGF-β1 and VEGF-A, to anti-Scl-70 antibodies, and to nailfold capillaroscopic abnormalities and pulmonary function tests. Results: Lower circulating uPA (3226 ± 2444 pg/mL) and increased higher PAI-1 (95.30 ± 22.80 ng/mL) and suPAR (2.522 ± 1.186 ng/mL by Human soluble uPAR ELISA; 3.835 ± 2.944 ng/mL by suPARnostic ELISA) levels were found in SSc patients. Both suPAR assays showed high sensitivity and specificity for SSc, but suPAR measured by the suPARnostic assay displayed stronger associations with clinical manifestations, indicating its potential as a marker of disease severity. uPA negatively correlated with TGF-β1 (p=0.008), whereas PAI-1 and suPAR (measured by suPARnostic assay) positively correlated with VEGF-A (p=0.01 and p=0.03, respectively). Furthermore, higher suPAR levels obtained by suPARnostic assay but not by Human suPAR ELISA were associated with microvascular and fibrotic manifestations. Conclusion: This preliminary study provides meaningful evidence supporting the potential of suPAR as a marker of disease severity in SSc and the impact of method-related differences in suPAR levels.
Keywords: Urokinase, Plasminogen activator inhibitor-1, Soluble urokinase plasminogen activator, systemic sclerosis, Fibrosis, Microvascular abnormalities
Received: 02 Sep 2025; Accepted: 14 Nov 2025.
Copyright: © 2025 Napolitano, Mormile, Mignogna, De Paulis, Rossi and Montuori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Francesca Wanda Rossi, francescawrossi@gmail.com
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