Endothelial Activation by aPL: A Potential Pathogenetic Mechanism for the Clinical Manifestations of the Syndrome

It is now generally accepted that antiphospholipid antibodies (aPL) rather than to be directed against PL themselves do recogize PL-binding proteins; beta sub(2)-Glycoprotein I ( beta sub(2)-GPI) has been shown to be the most important. beta sub(2)-Glycoprotein I is a highly cationic glycoprotein normally present in the serum and able to bind anionic structures including negatively charged PL. It displays several activities potentially related to the pathphysiology of the antiphospholipid symdrome (APS) by: (a) acting as a natural circulating anticoagulant, (b) potentiating platelet activation, and (c) interfering with the protein C/S system. More recently, beta sub(2)-GPI was found to adhere to human endothelial and trophoblast cell membranes and to offer suitable epitopes for circulating anti- beta sub(2)-GPI antibodies. The antibody binding to cell adhered beta sub(2)-GPI was shown to induce functional effects potentially related to the pathogenesis of the clinical manifestations of APS such as thrombotic events and fetal loss.