The molecular basis of antiphospholipid syndrome

Abstract

We herein review evidence that the phospholipid-binding protein β₂ glycoprotein-1 (β₂ GPI) is a causativeautoantigenin APS. Recent work suggeststhat the molecular regions in β₂ GPI that facilitate autoimmunization are those that promote binding to negatively charged phospholipids by means of strong positive (anionic) charge and hydrophobicity. Although many common infections can cause antiphospholipidantibodies 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 β₂ GPI. In peoplewho are susceptibleto APS, tolerance to self-β₂ GPI and phospholipidsis likely to be broken by foreign bacterial or viral proteins that contain such β₂ GPI-like epitopes.