Differential Constitutive Endothelial Dysfunction in Thrombotic and Obstetric Antiphospholipid Syndrome: A Study Using Patient-Derived Endothelial Colony-Forming Cells

BACKGROUND Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic and/or obstetric events and the presence of antiphospholipid antibodies (aPL). Endothelial dysfunction (ED), resulting from the interaction between aPL and endothelial cells, contributes to APS clinical features. However, it remains unclear whether constitutive ED predisposes to APS or differs between patients with thrombotic (T-APS) and obstetric (O-APS) manifestations. Endothelial Colony-Forming Cells (ECFCs), derived from patients, offer a valuable model to study ED in APS. AIMS • Evaluate constitutive ED in APS patients • Compare ED mechanisms in T-APS vs. O-APS METHODS ECFCs were isolated from primary APS (PAPS) patients stratified into T-APS and O-APS, and from healthy donors (HD). ED was assessed in ECFCs by evaluating early senescence, expression of pro-/anticoagulant molecules (flow cytometry), and thrombin generation (TGA). RESULTS ECFCs were isolated from all groups, showing similar early senescence rates. PAPS-ECFCs promoted faster thrombin generation and showed imbalanced pro-/anticoagulant profiles compared with HD. Among subgroups, only ECFCs from female T-APS patients showed significantly lower EPCR expression and enhanced thrombin generation than HD ECFCs. CONCLUSIONS PAPS-derived ECFCs display constitutive ED. T-APS patients, in particular, show reduced EPCR and increased thrombin generation, suggesting distinct endothelial features compared with O-APS. Further studies are ongoing to clarify the underlying mechanisms.