The Infectious Origin of the Anti-Phospholipid Syndrome

The anti-phospholipid syndrome (APS) is characterized by the development of thrombosis and pregnancy morbidity (mainly fetal losses) in the presence of anti-phospholipid antibodies (aPLs). These antibodies (Abs) are currently considered to be pathogenic autoantibodies directed mainly against phospholipid-binding proteins such as β2-glycoprotein-I (β2GPI). The factors causing the production of anti-β2GPI Abs remain unidentified, but an association with infectious agents has been reported. Studies of experimental APS models proved that molecular mimicry between β2GPI-related synthetic peptides and structures within bacteria, viruses, tetanus toxoid, and cytomegalovirus is a cause of experimental APS. The explanation of how microbial and viral infections might set off APS must take into account bystander activation, altered self-molecular changes, and a second hit, in addition to molecular mimicry. Basically, all individuals seem to harbor potentially autoreactive lymphocytes and Abs due to clonal escape as part of innate immunity. These cells or Abs remain innocuous unless activated by a pro-inflammatory microenvironment and/or a second hit on the proper genetic and epigenetic background. Herein, we discuss the association of aPLs in an infectious state, molecular mimicry as a proposed cause for the development of APS, and the contribution of databases to this topic.