- Oral presentation
- Open Access
Antiphospholipid antibodies and thrombosis: pathogenesis of antiphospholipid syndrome
Arthritis Res Ther volume 5, Article number: 28 (2003)
Antiphospholipid antibodies are present in a wide range of infectious and autoimmune diseases. Antiphospholipid antibodies, in particular anticardiolipin antibodies (aCL), lupus anticoagulants and antiprothrombin antibodies, are of considerable clinical importance because of the close association with predominant clinical features of venous and arterial thrombosis and pregnancy morbidity. The term antiphospholipid syndrome (APS) has been used to define this set of pathologic features. Recognition of this syndrome is now better understood worldwide as related clinical implications are now more well defined.
aCL found in APS patients are directed against phospholipid-binding plasma or serum proteins, in particular, β2-glycoprotein I (β2-GPI). Such aCL (anti-β2-GPI autoantibodies) recognized epitopes appearing on the β2-GPI molecule when β2-GPI interacts with a lipid membrane composed of negatively charged phospholipids or when β2-GPI is adsorbed on a polyoxygenated polystyrene plate treated with γ-irradiation or electrons.
Anti-β2-GPI antibodies have been found to activate endothelial cells by inducing a proinflammatory and procoagulant phenotype sustained by the upregulation of adhesion molecule (E-selectin, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1) expression, synthesis and secretion of cytokines, chemokines, endothelin-1 and tissue factor. Anti-β2-GPI antibody binding has been shown to induce NF-κB translation, leading to proinflammatory cell phenotypes similar to that elicited by interaction with lipopolysaccharide and proinflammatory cytokines (IL-1β, tumor necrosis factor alpha). Very recently, it was reported that anti-β2-GPI antibodies activate cells through the MyD88-dependent pathway, therefore implicating members of the Toll-like receptors family.
In this lecture, we will discuss the relation between the anti-β2-GPI antibodies, the Toll-like receptors/IL-1 receptor family on the cell surface and the pathogenesis of APS.
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Koike, T. Antiphospholipid antibodies and thrombosis: pathogenesis of antiphospholipid syndrome. Arthritis Res Ther 5, 28 (2003) doi:10.1186/ar829
- Arterial Thrombosis
- Vascular Cell Adhesion
- Lupus Anticoagulant
- Anticardiolipin Antibody
- Polystyrene Plate