Anti–β₂‐glycoprotein I antibodies induce monocyte release of tumor necrosis factor α and tissue factor by signal transduction pathways involving lipid rafts

Abstract

Anti-beta(2)GPI antibodies react with their target antigen, likely in association with annexin A2 and TLR-4, in lipid rafts in the monocyte plasma membrane. Anti-beta(2)GPI binding triggers IRAK phosphorylation and NF-kappaB translocation, leading to a proinflammatory and procoagulant monocyte phenotype characterized by the release of TNFalpha and TF, respectively. These findings provide new insight into the pathogenesis of APS, improving our knowledge of valuable therapeutic targets.