Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thromboembolism, obstetric complications, and the presence of antiphospholipid antibodies (aPL). Binding of aPL to the cell surface triggers their activation, leading to the release of extracellular vesicles (EVs). Medium/large vesicles of endothelial origin are most commonly studied in vitro as well as in plasma of APS patients. Other subtypes of vesicles and the group of small extracellular vesicles (sEVs) are less well understood in APS. The aim of this dissertation is to determine the importance of sEVs and their molecular profile in explaining the pathogenesis and heterogeneity of APS. In the plasma of thrombotic APS patients, we found increased levels of total sEVs, endothelial sEVs, and some sEV subtypes, indicating endothelial and platelet activation even in the absence of an acute thrombotic event. Although we did not detect increased levels of monocyte sEVs in APS, analysis of their cells of origin suggests monocyte activation. The increased surface expression of the integrin VLA4 on monocytes could be involved in the enhanced interaction between monocytes and the endothelium. Blocking this integrin could provide an alternative treatment option for more severe and difficult-to-treat APS patients in the future. Taken together, our results suggest that the profile of secreted sEVs is altered in patients with thrombotic APS, indicating their origin and the activation status of the cells of origin. Thus, we have shown that sEVs play an important role in APS, but further research is needed to more precisely define the effects of sEVs on endothelial cells, monocytes, and platelets and to better situate our findings in the pathogenesis of APS.
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