Recurrent Pregnancy Loss Causes, Controversies, and Treatment cap. 8 The Etiology of the Antiphospholipid Syndrome

Phospholipids (PL), the basic components of all cell membranes, consist of two layers. The inner layer contains negatively charged anionic alcohol groups facing the cytoplasm, and the outer layer contains neutral or zwitterionic alcohol groups facing the extracellular fluid or bloodstream. In certain conditions such as ischemia, cell injury, or autoimmunity, negatively charged PLs can be exteriorized. The exteriorized PLs may be an antigenic stimulus for the production of antiphospholipid antibodies (aPL) 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 and be presented to the immune system in unique “neoantigenic” conformations, which may induce aPL formation [1]. aPL may recognize either the PL region of the complex or an epitope consisting of the portion of the PL and neighboring aminoacyls on the protein carrier, or may react with the protein alone. In pregnancy, placental tissues are continuously remodeled resulting in the externalization of inner surface PLs such as phosphatidyl serine (PS) [2]. aPL require a cofactor (apolipoprotein H or β2GP1), a negatively charged phospholipid binding protein, to exert their effects. β2GP1-dependent aPL are thought to recognize their antigen on placental tissue, inhibit growth and differentiation of trophoblasts, and cause inflammation, defective angiogenesis, and thrombosis, leading to impaired placentation.