Phospholipid Binding Plasma Proteins Required for Antiphospholipid Antibody Detection—An Overview
John A. McIntyre PhD,
Dawn R. Wagenknecht,
Toshitaka Sugi,
Corresponding Author
John A. McIntyre PhD
Methodist Center for Reproduction and Transplantation Immunology, Indianapolis, IN
FRC Path, Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, 1701 N. Senate Blvd, Indianapolis, Indiana 46202Search for more papers by this authorDawn R. Wagenknecht
Methodist Center for Reproduction and Transplantation Immunology, Indianapolis, IN
Search for more papers by this authorToshitaka Sugi
Tokai University School of Medicine, Kanagawa, Japan
Search for more papers by this authorJohn A. McIntyre PhD,
Dawn R. Wagenknecht,
Toshitaka Sugi,
Corresponding Author
John A. McIntyre PhD
Methodist Center for Reproduction and Transplantation Immunology, Indianapolis, IN
FRC Path, Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, 1701 N. Senate Blvd, Indianapolis, Indiana 46202Search for more papers by this authorDawn R. Wagenknecht
Methodist Center for Reproduction and Transplantation Immunology, Indianapolis, IN
Search for more papers by this authorToshitaka Sugi
Tokai University School of Medicine, Kanagawa, Japan
Search for more papers by this authorAbstract
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 β2 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.
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