Phospholipid Binding Plasma Proteins Required for Antiphospholipid Antibody Detection-An Overview

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Abstract
Antibodies to phospholipid antigens (aPA) are associated with thrombosis thrombocytopenia and recurrent pregnancy loss. Contemporary data show many aPA target phospholipid-binding plasma proteins and not phospholipids. The purpose of this overview is to describe several phospholipid-binding proteins and provide data to demonstrate how the interaction between phospholipids and phospholipid binding proteins results in expression of neo-autoantigenic epitopes. Review of existing data. Illustrations of how certain plasma proteins beta 2 glycoprotein I, prothrombin, high and low molecular weight kininogens interact with the anionic phospholipids cardiolipin and phosphatidylserine and the zwitterionic phospholipid, phosphatidylethanolamine are shown and discussed. A model of aPA mediated thrombosis is presented. Some aPA recognize phospholipids directly, however, the majority and many which correlate with pathology target phospholipid binding proteins. Published data indicate that aPA represent a constellation of antibodies with multiple specificities. Insight into mechanisms responsible for aPA-associated thrombosis should provide a basis for treatment.