New Insights in the Pathophysiology of Antiphospholipid Syndrome

Abstract

The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by an elevated risk for arterial and venous thrombosis and pregnancy-related morbidity. Since the discovery of the disease in 1980s, numerous studies in cell culture systems, in animal models, and in patient populations have been reported, leading to a deeper understanding of the pathogenesis of APS. These studies have determined that circulating autoantibodies, collectively called antiphospholipid antibodies (aPL), the majority of which recognize cell surface proteins attached to the plasma membrane phospholipids, play a causal role in the development of the disease. The binding of aPL to the cell surface antigens triggers interaction of the complex with transmembrane receptors to initiate intracellular signaling in critical cell types, including platelets, monocytes, endothelial cells, and trophoblasts. Subsequent alteration of various cell functions results in inflammation, thrombus formation, and pregnancy complications. Apolipoprotein E receptor 2 (apoER2), a lipoprotein receptor family member, has been implicated as a mediator for aPL actions in platelets and endothelial cells. Nitric oxide (NO) is a signaling molecule known to exert potent antithrombotic, anti-inflammatory, and anti-atherogenic effects. NO insufficiency and oxidative stress have been linked to APS pathogenesis. This review will focus on the recent findings on how apoER2 and dysregulation of NO production contribute to aPL-mediated pathologies in APS.

Кардиоваскулярные Манифестации У Пациентов С Антифосфолипидным Синдромом: Вопросы Диагностики И Менеджмента

“…Вони включають сітчасте ліведо, тромбоцитопенію, Кумбс-позитивну гемолітичну анемію, антифосфоліпідну нефропатію, неврологічні прояви (хорея, поперечний мієліт, мігрені і когнітивна дисфункція, не обумовлена цереброваскулярними захворюваннями) і серцево-судинні прояви (частіше -ураження клапанів). Ці клінічні особливості пов'язані з циркулюванням аФЛ-АТ, які не завжди маніфестують тромбозами і акушерською патологією, а можуть бути пояснені такими механізмами, як запалення, активація комплементу і тромбоцитів [4,5].…”

Obstetric Anti-phospholipid Syndrome: State of the Art

“…The exact mechanisms involved in the prothrombotic state of the disease (causing thrombosis and/or obstetric complications) remain yet to be fully explained. aPL have the ability to induce thrombus formation in the arterial and/ or venous vasculature and/or microcirculation by targeting and affecting the functionality of a variety of cell types such as endothelial cells, monocytes, leukocytes, neutrophils, and platelets on the vascular aspect of the disease, and trophoblasts and decidual cells during gestation; the irregular function of these cells contributes in the disease development [9]. Several studies have reported that aPLs have the capacity to interact with the trophoblast and the endothelial cell monolayer, by disrupting the anticoagulant annexin A5 shield, resulting in fetal loss [10].…”

Recent Developments in Antiphospholipid Antibodies and the Antiphospholipid Syndrome

“…Sacharidou et al therefore summarize the currently available data on the pathophysiology of APS. 17 Evidence from in vitro studies and animal models support the notion that vascular cells are activated by the circulating aPL. Furthermore, Muller-Calleja and Lackner provide an overview of the current insights in the way target cells are activated by aPL and discuss the data that support the role for the various cellular receptors that have been implicated in the pathophysiology of the syndrome.…”