P25 Leukocyte cell surface expression of urokinase plasminogen activator receptor (uPAR) in patients with systemic lupus erythematosus

Objective The urokinase plasminogen activator receptor (uPAR) is crucial in efferocytosis and can be cleaved during inflammation, releasing soluble uPAR (suPAR). Previous research has shown an association between serum suPAR levels and irreversible organ damage in systemic lupus erythematosus (SLE).¹ However, naive leukocyte cell surface uPAR expression and its response to immune activation remain unknown. This study seeks to investigate uPAR leukocyte expression in patients with SLE and in healthy controls (HC), both under naive conditions and following immune stimulation. Methods The study has so far included 34 patients (28 females) classified according to the ACR and/or the SLICC criteria, and 21 healthy blood donors (17 females). Blood samples were stimulated with tumor necrosis factor (TNF) (n=53) or type I interferons (IFN-α-2b) (n=20) and analyzed by flow cytometry. Results Preliminary findings show slightly higher naive uPAR expression in patients with SLE (figure 1). Following TNF immune activation, significant uPAR upregulation is observed on neutrophils (65% increase in HC, p=0.0027; 30% increase in patients, p=0.002) and monocytes (52% increase in HC, p=1e⁻⁰⁶; 73% increase in patients, p=1e⁻⁰⁵). IFN-α activation increases uPAR expression on monocytes in both groups, while neutrophil expression remains stable in HC (3% increase) but rises by 16% in patients after stimulation. Additionally, there is a slight increase in neutrophil uPAR expression in patients with acquired organ damage, a slight elevation of uPAR leukocyte expression in patients without renal disorder versus those with renal disorder, and an elevated uPAR leukocyte expression in patients receiving prednisolone equivalents <5 mg compared to patients receiving ≥5 mg; however, none of these observations reach statistical significance (figure 2). Conclusion uPAR is upregulated on leukocytes after immune activation with both TNF and IFN-α. Interestingly, the IFN-α stimulated expression on neutrophils from patients was more pronounced compared with healthy controls. We further aim to compare the cellular expression of uPAR with levels of suPAR in plasma. Given the important role of uPAR in efferocytosis, an upregulated expression may relate to the accumulation of apoptotic cells seen in SLE. Reference Enocsson H, Wirestam L, Dahle C, et al. Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus. Journal of Autoimmunity 2020;106:102340.