Toll-like receptors play a crucial part in the pathophysiological activity of antiphospholipid antibodies.

Abstract

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis, recurrent fetal loss and the presence of a variety of antiphospholipid antibodies (aPL), directed to phospholipids like Cardiolipin and phospholipid binding proteins like β2-glycoprotein I. Till date, the pathophysiological processes underlying these thrombotic events were still not fully understood. Recent data support the idea that the aPL might act via enhanced cytokine release due to activation of certain Toll-like receptors. The investigation of some of those mechanisms in more detail enlightens the involvement of the intracellular receptors TLR7 and TLR8 in a central point. Using patients’ IgG fractions and/or monoclonal aPL, either generated from mouse or from human B-cells for the stimulation experiments of monocytes, endothelial cells or dendritic cells, all these stimuli induced an enhanced expression and secretion of cytokines, especially TNFα, caused by specific regulation or activation of Toll-like receptors. Using specific agonists or inhibitors could confirm the causal connection of these stimulatory effects. This review focuses on the recent developments connecting the binding of aPL with the activity of Toll-like receptors, especially in monocytes, endothelial cells and dendritic cells.