AB0081 ENDOTHELIAL MARKERS WITH DYSREGULATION IN SYSTEMIC LUPUS ERYTHEMATOSUS: A SYSTEMATIC LITERATURE REVIEW
Authors: S. Bergkamp, M. J. Wahadat, V. Smith, S. Kamphuis, J. M. Van den Berg, D. Schonenberg-Meinema
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic lupus erythematosus (SLE) is a severe, lifelong autoimmune disease known for its multisystem organ involvement. SLE patients are known to be at risk for premature atherosclerosis at a relatively young age (1). Endothelial dysregulation is one of the pathophysiologic mechanisms that can lead to the higher risk for cardiovascular disease in SLE (2). Multiple endothelial markers with dysregulation in SLE have been described so far, of which some are associated with disease activity. Objectives: To report a systematic literature review regarding endothelial markers that are dysregulated in SLE and search for associations with disease activity. Methods: The search was performed according to the Preferred Reporting Items for Systematic review and Meta-analysis Protocols (PRISMA-P) 2015 (3). In July 2020, the search terms were used in Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) published studies after the year 2000 that reported measurements of endothelial cell markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles and 3) disease activity measurement (i.e. SLEDAI, BILAG, SLAM, ECLAM or PGA). Exclusion criteria were 1) case reports or editorials, 2) studies performed in animals and 3) studies with microRNA/cytokine biomarkers. There was no minimum count for study population. The screening process is shown in figure 1. Results: From 1892 hits, we identified 110 eligible articles. Table 1 shows an overview of the most frequently studied endothelial markers. These identified endothelial markers are involved in endothelial cell (EC) activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. In most studies, dysregulation of the endothelial marker was associated with disease activity. The majority of the studies had a cross-sectional design, longitudinal data on endothelial markers in SLE are scarce. Conclusion: We identified multiple endothelial markers that are dysregulated in SLE and this dysregulation was often associated with disease activity in cross-sectional studies. Our future plan is to test the identified endothelial markers in (longitudinally collected) samples of (childhood onset) SLE patients, disease- and healthy controls. This will be a next step in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE-patients in young adulthood. Figure 1. References: [1]Vavlukis M, Pop-Gjorceva D, Poposka L, Sandevska E, Kedev S. Myocardial Infarction in Systemic Lupus Erythematosus - the Sex Specific Risk Profile. Curr Pharm Des. 2020 Dec 9. [2]Westerweel PE, Luyten RK, Koomans HA, Derksen RH, Verhaar MC. Premature atherosclerotic cardiovascular disease in systemic lupus erythematosus. Arthritis Rheum. 2007 May;56(5):1384-96. [3]Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015 Jan 2;350:g7647. Table 1. Endothelial marker Articles (no. of studies ) Significant correlation with SLEDAI (no. of studies ) Studies with control groups (no. of studies ) Longitudinal data (no. of studies ) Yes No Unknown Healthy controls Diseased controls VCAM-1 26 20 1 5 23 3 8 VEGF 22 13 5 4 20 2 2 ICAM-1 18 11 5 2 17 3 4 Thrombomodulin 17 10 5 2 13 2 2 E-Selectin 13 6 5 2 10 2 1 MCP-1 8 6 2 0 7 1 2 P-Selectin 6 3 2 1 6 1 1 IP-10 6 5 1 0 5 0 1 Pentraxin-3 5 5 0 0 5 1 2 vWF 5 4 1 0 5 0 2 Neopterin 3 2 1 0 2 0 2 Fas 3 0 2 1 2 0 1 Angiopoeietin-2 3 3 0 0 2 1 - Endothelin-1 3 1 2 0 3 0 - PAI-1 3 1 1 1 2 0 - Adrenomedullin 3 2 0 1 2 0 - TWEAK 3 1 1 1 1 2 - PECAM-1 3 1 1 1 3 0 - Disclosure of Interests: None declared