Etiology of Antiphospholipid Syndrome

Phospholipids consist of two layers and may be an antigenic stimulus to produce antiphospholipid antibodies (aPLs) or permit a number of serum proteins with procoagulant activity (β2-glycoprotein I [β2-GP1], prothrombin, protein C, protein S, and annexin V) to bind PL epitopes. Molecular mimicry between β2-GP1 bacterial and viral epitopes is the principal mechanism by which infectious agents induce production of aPL or antiphospholipid syndrome (APS) in genetically prone individuals. The most consistent genetic association is with HLA-DR4 and DRw53. The hypercoagulable state in APS involves platelets, endothelium, fibrinolysis, and the coagulation cascade. aPLs inhibit both protein C activation and the function of activated protein C. In animal models, following fetal resorption due to injection of human IgG with aPL activity, examination of the decidua revealed deposition of human IgG with mouse complement, neutrophil infiltration, and TNF secretion. In pregnant patients with APS and no other systemic autoimmune diseases, low serum of C3, C4 levels were reported to be associated with poor pregnancy outcome. Endometrial angiogenesis, decidualization, trophoblast invasion, and uterine vessel remodeling are all impaired in APS pregnancy loss. The negative role of multiple aPL positivity has been confirmed by several studies. The combination of triple aPL positivity represents the worst risk profile for adverse pregnancy outcome.