Autoantibodies with an apparent specificity for anionic phospholipids have been associated with a syndrome of thrombotic complications including thrombosis, recurrent fetal loss and thrombocytopenia. It has recently been established that a major target for these autoantibodies is actually the phospholipid binding plasma protein Beta2glyprotein I. Further, recent evidence suggest that Beta2glycoprotein I may bind the receptors on endothelial cells and/or platelets. A thrombotic diathesis may be created when autoantibodies bind to Beta2glycoprotein I while it is associated with endothelial cells or platelets. The thrombotic diathesis could arise if autoantibodies associated with Beta2glycoprotein I interfere with the protein C pathway on either of these two cells. We propose to examine the activity of Beta2glycoprotein I and autoantibodies to it in a cell based model system that mimics many aspects of physiologic coagulation. Further, we propose to examine the binding Beta2glycoprotein I to endothelial cells and show that it is not mediated solely by phospholipid. Since such binding would be mediated by a cellular receptor, we propose to isolate the receptor. These studies will help define the mechanisms that underlie the thrombotic diathesis of some of the lupus autoantibodies.
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