The Journey of Antiphospholipid Antibodies From Cellular Activation to Antiphospholipid Syndrome

Abstract

Pathogenic antiphospholipid antibodies (aPL) are the driving factors of recurrent pregnancy loss and thrombosis that characterize antiphospholipid syndrome (APS). Current evidence indicates that aPL induce a procoagulant phenotype in the vasculature and abnormal cellular proliferation and differentiation in placental tissues to cause the typical clinical features; however, the molecular mechanisms underlying these processes remain incompletely understood. Inflammation serves as a necessary link between the observed procoagulant phenotype and actual thrombus development and is an important mediator of the placental injury in APS patients. However, the underlying mechanisms for these events have also not been fully elucidated. In this review, we will outline the available data that give us our current understanding of the pathophysiology of APS, especially as it relates to the development of thromboembolic and obstetric pathological phenomena in these patients. We will also describe the intracellular signaling pathways activated by aPL in various cellular subtypes and outline the current evidence linking these pathways to clinical phenotypes. Finally, we will discuss the implications of distinct molecular patterns defining clinical phenotypes of APS patients.

Anti-phospholipid Antibodies and Smoking: An Overview

“…APS can occur on its own or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE) [2]. A combination of genetic and environmental factors is thought to be responsible for the formation of these antibodies [3]. The diagnosis of APS requires (1) one or more specific clinical events such as a vascular thrombosis and/or an adverse obstetric event and (2) the confirmed presence of a repeatedly positive aPL [4].…”

Anticardiolipin antibodies in concurrent poststreptococcal glomerulonephritis and autoimmune hemolytic anemia: A case report

“…These antibodies have been hypothesized to have the potential to exacerbate inflammation-mediated tissue injury. 15 However, Ardiles et al found no difference of degree of renal injury, glomerular abnormalities in urine and creatinine levels in clinical follow-up between aCL-positive patients and aCL-negative patients with APSGN. 2 It is considered that aCL can be associated with a thrombotic risk if persistently elevated.…”

Anticuerpos contra la cardiolipina en glomerulonefritis postestreptocócica concurrente con anemia hemolítica autoinmunitaria: a propósito de un caso

“…Se ha propuesto la hipótesis de que estos anticuerpos podrían potencialmente exacerbar la lesión tisular mediada por la inflamación. 15 Sin embargo, Ardiles y col. no hallaron diferencias en el grado de lesión renal, en las anomalías glomerulares en la orina ni en la concentración de creatinina durante el seguimiento clínico de los pacientes con GNAPE que tenían resultados positivos para los anticuerpos contra la cardiolipina y aquellos con resultados negativos. 2 Se considera que los anticuerpos contra la cardiolipina pueden estar asociados con un riesgo de trombosis si permanecen elevados.…”