Tests & Clinical Applications, Antiphospholipid syndrome, What is the origin of the disease?
The antibodies present are not directed against phospholipids but against various proteins able to bind to phospholipids, chiefly ß2-glycoprotein-1 (ß2GPI).
Many bacterial infections are accompanied by increased synthesis of antiphospholipid antibodies, and, in rare cases, clinical signs of APS. These antibodies are synthesised by B lymphocytes as a reaction to epitopes present in infectious agents. Other environmental factors, such as the use of certain drugs or the presence of cancer, may be associated with increased numbers of such antibodies.
Another hypothesis involves the synthesis of natural antibodies in response to infection that become pathogenic under certain unfavourable conditions such as oxidative stress.
Antiphospholipid antibodies have been shown to be present in 12% of elderly subjects and 2% of subjects in younger populations.
Genetics and APS
The presence of antiphospholipid antibodies is associated, at least in part, with a genetic predisposition via the HLA system.
In addition, an association between certain polymorphisms of ß2-GPI gene (Val/Leu 247) and the development of APS has been suggested.
The pathogenic role of antiphospholipid antibodies
ß2-GPI is a plasma protein of which the physiological role remains unknown. It binds to negatively-charged phospholipids such as cardiolipin, phosphatidylserine and phosphatidylinositol. In binding to phospholipids, ß2-GPI changes its conformation and presents a cryptic epitope to which antibodies may bind.
Antiphospholipid antibodies can affect haemostatic equilibrium through their interaction in pro- and anti-coagulation physiological reactions. They can also bind to various types of cells such as endothelial cells, monocytes and platelets. In addition, these antibodies are seemingly able to interact with trophoblast cells.
Antiphospholipid antibodies induce an inflammatory state in the endothelium, thereby activating the complement system. Finally, cellular activation is accompanied by release of microparticles into the circulation.