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. 2022 Dec 1;12(12):1984.
doi: 10.3390/jpm12121984.

The Association of uPA, uPAR, and suPAR System with Inflammation and Joint Damage in Rheumatoid Arthritis: suPAR as a Biomarker in the Light of a Personalized Medicine Perspective

Maurizio Benucci  1 , Arianna Damiani  2 , Edda Russo  2 , Serena Guiducci  2 , Francesca Li Gobbi  1 , Paola Fusi  1 , Valentina Grossi  3 , Amedeo Amedei  2 , Mariangela Manfredi  3 , Maria Infantino  3
Affiliations

The Association of uPA, uPAR, and suPAR System with Inflammation and Joint Damage in Rheumatoid Arthritis: suPAR as a Biomarker in the Light of a Personalized Medicine Perspective

Maurizio Benucci et al. J Pers Med. .

Abstract

Background: In recent years, the involvement of the soluble urokinase Plasminogen Activator Receptor (suPAR) in the pathophysiological modulation of Rheumatoid Arthritis (RA) has been documented, resulting in the activation of several intracellular inflammatory pathways.

Methods: We investigated the correlation of urokinase Plasminogen Activator (uPA)/urokinase Plasminogen Activator Receptor (uPAR) expression and suPAR with inflammation and joint damage in RA, evaluating their potential role in a precision medicine context.

Results: Currently, suPAR has been shown to be a potential biomarker for the monitoring of Systemic Chronic Inflammation (SCI) and COVID-19. However, the effects due to suPAR interaction in immune cells are also involved in both RA onset and progression. To date, the literature data on suPAR in RA endorse its potential application as a biomarker of inflammation and subsequent joint damage.

Conclusion: Available evidence about suPAR utility in the RA field is promising, and future research should further investigate its use in clinical practice, resulting in a big step forward for precision medicine. As it is elevated in different types of inflammation, suPAR could potentially work as an adjunctive tool for the screening of RA patients. In addition, a suPAR system has been shown to be involved in RA pathogenesis, so new data about the therapeutic response to Jak inhibitors can represent a possible way to develop further studies.

Keywords: disease activity score; rheumatoid arthritis; suPAR; systemic chronic inflammation; uPA/uPAR.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the urokinase plasminogen activation (uPA) system. D1, D2, and D3 represents the three domains of the protein. The red line represents the linker region between D1 and D2–D3 domains. Active uPA cleaves plasminogen to plasmin that activates matrix metalloproteases (MMPs degrade fibrin), cleaves extracellular matrix (ECM) components, and activates the complement pathway.
Figure 2
Figure 2
Immune cells producing uPA/uPAR as articular chondrocytes, neutrophils, monocytes, FLS, and endothelial cells produce high amounts of uPA in the RA microenvironment during RA disease condition, promoting articular damage, synovial infiltration, and phlogosis in the joint.
See this image and copyright information in PMC

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