POS0289 NOVEL ENDOTHELIAL PROGENITOR CELLS POPULATIONS AS BIOMARKERS OF DAMAGE AND REMISSION IN SYSTEMIC LUPUS ERYTHEMATOSUS.
Authors: S. García, C. Rafael Vidal, B. Malvar-Fernández, S. Martínez-Ramos, I. Altabás González, C. Mouriño Rodríguez, J. M. Pego-Reigosa
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Endothelial progenitor cells (EPCs) are essential for maintenance of vascular homeostasis and stability, which are key processes in the pathogenesis of systemic lupus erythematosus (SLE). The frequency and function of EPCs in SLE pathogenesis is controversial, since several works reported an increase in EPCs populations in patients with SLE compared to healthy controls (HC) [1], while others showed no differences [2] or even a decrease [3]. Given the contradictory results, in this study we have used novel flow cytometry tools for the identification of EPCs specific subpopulations in patients with SLE and we have explored their association with the clinical characteristics. <h3>Objectives:</h3> The objective of this work was to identify EPCs specific subpopulations in patients with SLE using a novel flow cytometry tool. <h3>Methods:</h3> Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SLE and healthy controls (HC). mRNA and surface protein expression were determined by quantitative PCR (qPCR) and flow cytometry. Clusters identification and characterization were performed using tSNE-CUDA dimensionality reduction algorithms. <h3>Results:</h3> tSNE-CUDA analysis identified eight different clusters in PBMCs from HC and patients with SLE. Three of these clusters had EPCs-like phenotype and the expression was elevated in patients with SLE. Among these clusters, only cluster 6 was significantly elevated in patients with SLE (Figure 1A-C). Moreover, four SLE-associated subclusters were found mainly expressed in patients with SLE, being only present in patients in remission with SLE and significantly associated with the 2021 Definition of Remission in SLE (Figure 1D–F). Importantly, we also identified specific clusters in SLE patients with organ damage, according to the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI). These clusters showed an EPCs-like phenotype, but the expression of angiogenic markers was lower compared to HC or patients without organ damage, suggesting an impaired angiogenic function (Figure 2). <h3>Conclusion:</h3> Our novel approach identified clusters of EPCs in patients with SLE that are associated with remission and damage. Therefore, these clusters might be useful biomarkers to predict disease progression and severity in SLE pathogenesis. <h3>REFERENCES:</h3> [1] Rodríguez-Carrio, J. <i>et al.</i> Circulating endothelial cells and their progenitors in systemic lupus erythematosus and early rheumatoid arthritis patients. <i>Rheumatology (United Kingdom</i>) <b>51</b>, 1775–1784 (2012). [2] Grisar, J. <i>et al.</i> Systemic lupus erythematosus patients exhibit functional deficiencies of endothelial progenitor cells. <i>Rheumatology</i><b>47</b>, 1476–1483 (2008). [3] Lee, P. Y. <i>et al.</i> Type I interferon as a novel risk factor for endothelial progenitor cell depletion and endothelial dysfunction in systemic lupus erythematosus. <i>Arthritis Rheum</i><b>56</b>, 3759–3769 (2007). <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>