Microparticles: An Alternative Explanation to the Behavior of Vascular Antiphospholipid Syndrome

Abstract

Antiphospholipid syndrome is an autoimmune disease characterized by the persistent presence of antiphospholipid antibodies, along with occurrence of vascular thrombosis and pregnancy morbidity. The variety of antiphospholipid antibodies and their related mechanisms, as well as the behavior of disease in wide groups of patients, have led some authors to propose a differentiation of this syndrome into two independent entities: vascular and obstetric antiphospholipid syndrome. Thus, previous studies have discussed whether specific autoantibodies may be responsible for this differentiation or, in contrast, how the same antibodies are able to generate two different clinical presentations. This discussion is yet to be settled. The capability of serum IgG from patients with vascular thrombosis to trigger the biogenesis of endothelial cell-derived microparticles in vitro is one of the previously discussed differences between the clinical entities of antiphospholipid syndrome. These vesicles constitute a prothrombotic mechanism as they can directly lead to clot activation in murine models and recalcified human plasma. Nevertheless, other indirect mechanisms by which microparticles can spread a procoagulant phenotype could be critical to understanding their role in antiphospholipid syndrome. For this reason, questions regarding the cargo of microparticles, and the signaling pathways involved in their biogenesis, are of interest in attempting to explain the behavior of this autoimmune disease.

Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome

“…(2) decreased bioavailability of nitric oxide (NO); (3) enhanced synthesis of vasoconstrictor factors, such as endothelin-1; (4) adhesion molecule synthesis; and (5) the release of endothelial microparticles (Mayer-Pickel et al, 2016;Engel et al, 2017;Sacharidou et al, 2018;Miranda et al, 2019;Velasquez et al, 2019;Alvarez et al, 2021). These pathological effects are induced by beta 2-glycoprotein-I (β2GPI) bound to the endothelium, but this mechanism is unclear.…”

“…Contrarily, patients with obstetric APS who have pregnancy morbidity plus thrombosis and high aPL titers, particularly those with triple aPL positivity, have an ineffective standard of care, but the addition of hydroxychloroquine (HCQ) improves the gestational outcome ( De Carolis et al, 2017 ; Ruffatti et al, 2017 ; Mekinian et al, 2018 ). aPL in these patients lead to endothelial activation and dysfunction, which deteriorate vascular relaxation through diverse mechanisms, including (1) the production of reactive oxygen species (ROS); (2) decreased bioavailability of nitric oxide (NO); (3) enhanced synthesis of vasoconstrictor factors, such as endothelin-1; (4) adhesion molecule synthesis; and (5) the release of endothelial microparticles ( Mayer-Pickel et al, 2016 ; Engel et al, 2017 ; Sacharidou et al, 2018 ; Miranda et al, 2019 ; Velasquez et al, 2019 ; Alvarez et al, 2021 ). These pathological effects are induced by beta 2-glycoprotein-I (β2GPI) bound to the endothelium, but this mechanism is unclear.…”