Phospholipid binding plasma proteins required for antiphospholipid antibody detection--an overview

Abstract

Problem: 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.

Method: Review of existing data.

Results: 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.

Conclusions: 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.