Mechanism of action of beta2-glycoprotein I-dependent lupus anticoagulants.
There is accumulating evidence showing that lupus anticoagulants (LA) are more strongly associated with thrombosis than anticardiolipin antibodies. In addition, indirect evidence has been presented indicating that beta2GPI-dependent LA are more strongly associated with thrombosis than prothrombin-dependent LA. From this, one may assume that anti-beta2GPI antibodies with LA activity are more pathogenic than anti-beta2GPI antibodies without LA activity. Therefore, it is of the utmost importance to understand the molecular basis on which some anti-beta2GPI antibodies behave as LA. In this presentation, the current knowledge on the interaction of beta2GPI with phospholipids and with anti-beta2GPI antibodies is reviewed and an integrated model for the anti-beta2GPI-dependent LA activity is proposed with implications for a pathogenic role of these particular antibodies.
Arnout
J
J
Center for Molecular and Vascular Biology, University of Leuven, Belgium. jef.arnout@med.kuleuven.ac.be
Vermylen
J
J
D000818:Animals; D000838:Anions; D017153:Antibodies, Anticardiolipin / Q000276:immunology; D000915:Antibody Affinity; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D016682:Lupus Coagulation Inhibitor / Q000276:immunology* / Q000378:metabolism; D046911:Macromolecular Substances; D008322:Mammals / Q000378:metabolism; D018448:Models, Immunological; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D053482:beta 2-Glycoprotein I
D000838:Anions; D017153:Antibodies, Anticardiolipin; D001324:Autoantigens; D000939:Epitopes; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D016682:Lupus Coagulation Inhibitor; D046911:Macromolecular Substances; D010743:Phospholipids; D053482:beta 2-Glycoprotein I