The molecular basis of antiphospholipid syndrome

We herein review evidence that the phospholipid-binding protein β 2 glycoprotein-1 (β 2 GPI) is a causative autoantigen in APS. Recent work suggests that the molecular regions in β 2 GPI that facilitate autoimmunization arethose that promote binding to negatively charged phospholipids by means of strong positive (anionic) charge and hydrophobicity. Although many common infections can cause antiphospholipid antibodies to be produced in humans, such postinfectious aPL are rarely associated with thromboses or pregnancy morbidity, the central features of antiphospholipid syndrome (APS). We propose that the causes of APS include those infectious agents that mimic the above molecular domains in β 2 GPI. In people who are susceptible to APS, tolerance to self-β 2 GPI and phospholipids is likely to be broken by foreign bacterial or viral proteins that contain such β 2 GPI-like epitopes.