Immunopathogenesis of the antiphospholipid antibody syndrome: an update.
The primary antiphospholipid antibody syndrome is characterized clinically by the presence of venous and arterial thrombosis, recurrent fetal loss, and thrombocytopenia. The presence of antiphospholipid antibodies is a central serologic finding in primary antiphospholipid antibody syndrome, and plays a critical role in diagnosis. Contrary to initial reports, it is now widely accepted that these autoantibodies are directed predominantly against two antigens: phospholipid-binding plasma protein beta2-glycoprotein I and prothrombin. The mechanism by which antiphospholipid antibodies cause disease is under vigorous investigation. It is hypothesized that antiphospholipid antibodies induce a procoagulant state by binding to antigens on endothelial cells and trophoblast cell surfaces. Indeed, beta2-glycoprotein I appears to function as a cofactor that facilitates this interaction. The resulting endothelial cell activation is associated with cell-surface expression of adhesion molecules that lead to monocyte adhesion - the first steps in thrombosis. Although the precise mechanism that mediates endothelial cell-platelet interaction have not been fully elucidated, platelet binding to the endothelium appears to be the next phase in thrombosis. Thus, the antiphospholipid antibody may be a triggering or activating factor in placental spiral artery thrombosis and subsequent placental infarction. More recently, a role for annexin V has emerged. Studies suggest that thrombosis in the antiphospholipid syndrome may be due to disruption of the annexin shield by antiphospholipid (and cofactor) antibodies, which results in the increased exposure of trophoblasts and endothelial cells to thrombogenic phospholipids.
Singh
A K
AK
Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. asingh@partners.org
D017152:Antibodies, Antiphospholipid / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000209:etiology / Q000276:immunology*; D006801:Humans; D013927:Thrombosis / Q000276:immunology
D017152:Antibodies, Antiphospholipid