Abstract
The antiphospholipid syndrome is characterized by antibodies directed against phospholipid-binding
proteins and phospholipids attached to cell membrane receptors, mitochondria, oxidized
lipoproteins, and activated complement components. When antibodies bind to these complex
antigens, cells are activated and the coagulation and complement cascades are triggered,
culminating in thrombotic events and pregnancy morbidity that further define the syndrome.
The phospholipid-binding proteins most often involved are annexins II and V, β2-glycoprotein I, prothrombin, and cardiolipin. A distinguishing feature of the antiphospholipid
syndrome is the “lupus anticoagulant.” This is not a single entity but rather a family
of antibodies directed against complex antigens consisting of β2-glycoprotein I and/or prothrombin bound to an anionic phospholipid. Although these
antibodies prolong in vitro clotting times by competing with clotting factors for
phospholipid binding sites, they are not associated with clinical bleeding. Rather,
they are thrombogenic because they augment thrombin production in vivo by concentrating
prothrombin on phospholipid surfaces. Other antiphospholipid antibodies decrease the
clot-inhibitory properties of the endothelium and enhance platelet adherence and aggregation.
Some are atherogenic because they increase lipid peroxidation by reducing paraoxonase
activity, and others impair fetal nutrition by diminishing placental antithrombotic
and fibrinolytic activity. This plethora of destructive autoantibodies is currently
managed with immunomodulatory agents, but new approaches to treatment might include
vaccines against specific autoantigens, blocking the antibodies generated by exposure
to cytoplasmic DNA, and selective targeting of aberrant B-cells to reduce or eliminate
autoantibody production.
Keywords
antiphospholipid antibodies - phospholipid-binding proteins - lupus anticoagulant
