SYNCHRONIZED INHIBITION OF THE PHOSPHOLIPID MEDIATED AUTOACTIVATION OF FACTOR-XII IN PLASMA BY BETA(2)-GLYCOPROTEIN-I AND ANTI-BETA(2)-GLYCOPROTEIN-I

Lupus anticoagulants are a group of antibodies commonly found in patie nts with autoimmune diseases such as systemic lupus erythematosus. Lup us anticoagulants inhibit phospholipid dependent coagulation and may b ind to negatively charged phospholipids. Recent studies have suggested an association between anti-beta(2)-glycoprotein I and a lupus antico agulant, whose activity is frequently dependent on the presence of bet a(2)-glycoprotein I. Based on these observations, the effect of anti-b eta(2)-glycoprotein I on the autoactivation of factor XII in plasma wa s investigated. Autoactivation initiated by the presence of negatively charged phospholipids, but not by sulfatide, was strongly inhibited b y immunoaffinity purified anti-beta(2)-glycoprotein I, The dose-respon se curve of anti-beta(2)-glycoprotein I was identical with that of a p recipitating 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 w as observed. This increase was of the same magnitude as the decreased rate observed in plasma supplemented with the same amount of beta(2)-g lycoprotein I as in the plasma itself. This confirms the inhibitory ef fect of beta(2)-GP-I on the contact activation and shows that inhibiti on is effective on the autoactivation of factor XII in plasma, The inh ibitory action of beta(2)-glycoprotein I was independent of the inhibi tion caused by the anti-beta(2)-glycoprotein I/beta(2)-glycoprotein I complex suggesting a synchronized inhibition of factor XII autoactivat ion by beta(2)-glycoprotein I and anti-beta(2)-glycoprotein I. The inh ibition 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 lup us anticoagulant.