This project will help delineate the true nature of antigens in antiphospholipid syndrome (APS). Application of this knowledge would accelerate the pace of basic and clinical research as well as benefit tens of thousands of U.S. patients each year. Primary APS in some severe cases leads to death via emergency venous thrombosis/embolism;and secondary APS compounds other autoimmune diseases such as lupus and venous thromboembolism. Women with APS are at higher risk for preeclampsia, preterm birth, and recurrent pregnancy loss. Great progress has been made in understanding APS, but there remains conflicting data and many questions. Diagnosis of APS is complicated due to the heterogeneity of types of autoantibodies produced and their specific target antigens. We propose Phase I research to better define the dominant phospholipid epitope(s) important in APS, recurrent pregnancy loss, and venous thrombosis. Our system uses pure synthetic phospholipids to create chemically defined homogenous surfaces towards the goal of determining pathogenic epitopes and characterizing the clinically relevant antibodies that bind to these determinants. We envision simplified and multiplex lab assays for rapid typing and quantification of anti-phospholipid antibodies in patients suspected of APS including specific biomarker signatures for obstetric, hemostasis, and other autoimmune conditions. Our four specific aims are: (i) Synthesize biotinylated phospholipids including a rare lipid implicated in APS (ii) Collect and bank serum samples from control, APS, recurrent pregnancy loss, and venous thrombosis patients (iii) Construct an ELISA to measure anti-monolysocardiolipin antibodies (iv) Multiplex important APS phospholipids to obtain disease-selective biomarker signatures from a single sample measurement Dr. Paul Neilsen, Ph.D. (Echelon Biosciences) is an experienced Principal Investigaator with more than ten years practice successfully combining lipid synthesis and biochemical assay development. Dr. D. Ware Branch, M.D. (University of Utah) is a world-renowned clinical researcher specializing in treating pregnant women who suffer from APS and recurrent pregnancy loss. With the addition of Dr. Matthew Rondina, M.D. the Co-Director for University Healthcare Thrombosis Services, the team is assembled and enthusiastically anticipates the opportunity to execute the project aims. This project and work will extend beyond the immediate funding period to have a positive impact on APS researchers, physicians, and patients suffering from these debilitating autoimmune diseases.
Disorders arising from autoantibodies to phospholipids are a significant health burden especially in women and when combined with other autoimmune diseases. This project will help define the biochemical causes of antiphospholipid disorders and improve their diagnosis bringing better understanding and diagnosis to researchers, physicians, and patients.
|Freeman, Andrew L; Pendleton, Robert C; Rondina, Matthew T (2010) Prevention of venous thromboembolism in obesity. Expert Rev Cardiovasc Ther 8:1711-21|