Antiphospholipid antibodies: biological basis and prospects for treatment

Antiphospholipid antibodies (aPL) are autoantibodies that are associated with recurrent reproductive failure and thrombotic disease. There are two well-characterised aPL, lupus anticoagulant and anticardiolipin antibodies. aPL were originally thought to bind to negatively-charged phospholipids but it is now clear that the title aPL is a misnomer and that the antigens for these autoantibodies are actually phospholipid-binding proteins. Chief amongst these phospholipid-binding proteins are prothrombin and beta(2) glycoprotein I. This review concentrates on the role of beta(2) glycoprotein I in the reproductive failure caused by aPL. Exactly how aPL cause reproductive failure remains unknown but there is emerging evidence that the antibodies may have several different adverse effects on trophoblasts. There is also evidence questioning the traditional hypothesis that fetal demise is secondary to thrombosis of the utero-placental circulation. Heparin is commonly used to treat pregnant women with aPL but if these antibodies do not cause fetal demise primarily by a thrombotic mechanism a question must be raised over the role of heparin. However, heparin binds to many proteins including beta(2) glycoprotein I and it is possible that the reported beneficial effects of heparin in aPL-affected pregnancies may be due to the ability of heparin to prevent the interaction of aPL and beta(2) glycoprotein I.