title: Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I.
abstract: Lupus anticoagulants are a group of antibodies commonly found in patients with autoimmune diseases such as systemic lupus erythematosus. Lupus anticoagulants inhibit phospholipid dependent coagulation and may bind to negatively charged phospholipids. Recent studies have suggested an association between anti-beta 2-glycoprotein I and a lupus anticoagulant, whose activity is frequently dependent on the presence of beta 2-glycoprotein I. Based on these observations, the effect of anti-beta 2-glycoprotein I on the autoactivation of factor XII in plasma was investigated. Autoactivation initiated by the presence of negatively charged phospholipids, but not by sulfatide, was strongly inhibited by immunoaffinity purified anti-beta 2-glycoprotein I. The dose-response curve of anti-beta 2-glycoprotein I was identical with that of a precipitating antibody, showing no inhibition at low and high antibody dilutions and maximal inhibition at an intermediate dilution. At high antibody concentrations, an increased rate of factor XIIa activation was observed. This increase was of the same magnitude as the decreased rate observed in plasma supplemented with the same amount of beta 2-glycoprotein I as in the plasma itself. This confirms the inhibitory effect of beta 2-GP-I on the contact activation and shows that inhibition is effective on the autoactivation of factor XII in plasma. The inhibitory action of beta 2-glycoprotein I was independent of the inhibition caused by the anti-beta 2-glycoprotein I/beta 2 glycoprotein I complex suggesting a synchronized inhibition of factor XII autoactivation by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. The inhibition caused by the antibody is suggested to be caused by a reduced availability of negatively charged phospholipids due to the binding of the anti-beta 2-GP-I/beta 2-GP-I complex. This complex may be a lupus anticoagulant.
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D002863:Chromogenic Compounds; D004306:Dose-Response Relationship, Immunologic; D004789:Enzyme Activation / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D005174:Factor XII / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015956:Factor XIIa / Q000032:analysis* / Q000096:biosynthesis; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000276:immunology / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000494:pharmacology; D010743:Phospholipids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D053482:beta 2-Glycoprotein I
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D002863:Chromogenic Compounds; D000939:Epitopes; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D018129:Phosphatidylinositol Phosphates; D010743:Phospholipids; D013433:Sulfoglycosphingolipids; D053482:beta 2-Glycoprotein I; D005174:Factor XII; D015956:Factor XIIa