Circulating Endothelial Cells are Associated with Thromboembolic Events in Patients with Antiphospholipid Antibodies

Abstract

Background: Endothelium damage has been described in antiphospholipid antibodies (aPL) positive patients. However, it is uncertain whether circulating endothelial cells (CECs) – which are released when endothelial injury occurs – can identify patients at high risk for thrombosis. Methods: Ninety-seven patients with aPL and/or Systemic Lupus Erythematosus (SLE) were included. CECs were determined by an automated CellSearch® system. We also assayed plasma levels of tissue factor-bearing extracellular vesicles (TF+/EVs) and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) as markers of endothelial dysfunction/damage. Results: Patients mean age was 46.1±13.9 years, 77 were women. Thirty-seven had SLE and 75 patients were suffering from antiphospholipid syndrome. Thirty-seven percent of patients presented a medical history of arterial thrombosis and 46% a history of venous thromboembolism (VTE). Thirteen patients had increased levels of CECs (>20/mL), with a mean CEC level of 48.3±21.3 per mL. In univariate analysis, patients with obesity or medical history of myocardial infarction (MI), VTE or nephropathy had a significant increased CECs level. In multivariate analysis, obesity (OR=6.07 [95% CI; 1.42-25.94]), VTE (OR=7.59 [95% CI; 1.38-41.66]), and MI (OR=5.5 [95% CI;1.1-26.6)] were independently and significantly associated with elevated CECs. We also identified significant correlations between CECs and other markers of endothelial dysfunction: sTREM-1 and TF+/EVs. Conclusions: This study demonstrated that endothelial injury assessed by the levels of CECs was associated with thromboembolic events in patients with aPL and/or autoimmune diseases.

An update on inflammation in antiphospholipid syndrome

“…The stressed or injured endothelium releases CECs and extracellular vesicles, both of which are elevated in APS [29,30]. A 2022 study quantified CECs from the blood of patients with aPL and/or SLE and found that patients with a history of obesity, myocardial infarction, venous thromboembolism, or nephropathy had more CECs in circulation [31 ▪▪ ]. Additionally, the study also showed a significant correlation between CECs and other markers likely to be associated with endothelial dysfunction, including tissue factor-bearing extracellular vesicles and soluble TREM-1 (triggering receptor expressed on myeloid cells-1) [31 ▪▪ ].…”