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 defined by thrombotic (T-APS) or obstetric (O-APS) events in the presence of antiphospholipid antibodies (aPLs). Endothelial dysfunction (ED), due to aPL–endothelium interaction, contributes to APS manifestations. However, whether constitutive ED predisposes to disease onset and clinical phenotype remains unclear. In this context, patient-specific endothelial colony-forming cells (ECFCs) represent a valuable tool to investigate ED in APS. AIM To assess constitutive ED in primary T-APS and O-APS patients and define its pathogenic mechanisms. METHODS ECFCs were isolated from T-APS, O-APS patients and healthy donors (HD).1 ED was assessed by evaluating ECFC early senescence rate, expression of pro-/anticoagulant molecules, and prothrombotic potential.2 RESULTS ECFCs were obtained from all groups, showing similar early senescence rates. PAPS ECFCs showed accelerated thrombin generation and imbalance between pro- and anticoagulation factors compared with HD ECFCs. Among subgroups, only ECFCs from female T-APS patients had lower EPCR expression and significantly enhanced thrombin generation than HD ECFCs. CONCLUSIONS These findings indicate that ECFCs from primary APS patients exhibit constitutive ED. Moreover, T-APS and O-APS appear to display distinct endothelial profiles, with T-APS patients showing a marked prothrombotic shift. Further analyses are ongoing to better understand mechanisms underlying these differences.