Antiphospholipid antibodies or not?: The role of β2 glycoprotein 1 in autoantibody-mediated pregnancy loss

Antiphospholipid antibodies are a family of autoantibodies including lupus anticoagulant and anticardiolipin antibodies that appear to react with negatively charged phospholipids. These antibodies induce trhombosis and pregnancy complications including recurrent stillbirth, recurrent miscarriage, pre-eclampsia and intra-uterine growth retardation. Recent evidence indicates that antiphospholipid antibodies do not bind directly to phospholipid but rather to phospholipid-binding proteins or to a combination of phospholipid and phospholipid-binding proteins. This opens the possibility that antiphospholipid antibodies may be pathogenic by disrupting the function of phospholipid-binding proteins rather than membrane phospholipid. The antigenic role of one phospholipid-binding protein, beta(2) glycoprotein, has been studied in the greatest detail and is reviewed. Despite being highly conserved and expressed at high levels, the physiological function of beta(2) glycoprotein 1 remains unknown. However, a number of putative roles have been proposed which allow speculation as to the mechanism by which antiphospholipid antibodies may disrupt haemostasis and pregnancy. (C) 1997 Elsevier Science Ireland Ltd.