Anti-Phospholipid Multiplex For Pathologic Epitopes

描述(由申请人提供)：该项目将有助于描述抗磷脂综合征(APS)中抗原的真实性质。这一知识的应用将加快基础和临床研究的步伐，并使每年数以万计的美国患者受益。 在一些重症病例中，原发APS通过紧急静脉血栓/栓塞导致死亡；继发APS与其他自身免疫性疾病，如狼疮和静脉血栓栓塞症复合。患有APS的妇女患先兆子痫、早产和反复妊娠丢失的风险更高。对APS的认识已经取得了很大的进展，但仍然存在相互矛盾的数据和许多问题。由于产生的自身抗体类型及其特异性靶抗原的异质性，APS的诊断很复杂。我们建议进行第一阶段的研究，以更好地确定主要的磷脂表位(S)在急性胰腺炎、复发性妊娠丢失和静脉血栓形成中的重要作用。我们的系统使用纯合成磷脂来创建化学定义的均一表面，以实现确定致病表位和表征与这些决定因素结合的临床相关抗体的目标。 我们设想简化和多样化的实验室检测方法，用于对疑似APS患者的抗磷脂抗体进行快速分型和定量，包括产科、止血和其他自身免疫疾病的特定生物标记物标记。我们的四个具体目标是： (I)合成生物素化磷脂，包括一种与黄曲霉毒素有关的稀有脂质 (Ii)收集和储存对照组、黄体生成素综合征、反复妊娠丢失和静脉血栓形成患者的血清样本 (Iii)建立检测抗单溶心磷脂抗体的酶联免疫吸附试验 (Iv)复合重要的APS磷脂，以从单一样本测量中获得疾病选择性生物标志物特征 Paul Neilsen博士(梯队生物科学)是一位经验丰富的首席研究员，拥有十多年的实践经验，成功地将脂肪合成和生化分析开发结合在一起。Ware Branch博士，医学博士(犹他大学)，是世界著名的临床研究人员，专门治疗患有APS和反复妊娠丢失的孕妇。随着大学医疗保健血栓服务联席主任Matthew Rondina博士的加入，团队已经组建起来，并热情地期待着有机会实现项目目标。这一项目和工作将超越直接的资助期，对APS的研究人员、医生和患有这些衰弱的自身免疫性疾病的患者产生积极影响。 公共卫生相关性：磷脂自身抗体引起的疾病是一个重大的健康负担，特别是在妇女中，当与其他自身免疫性疾病结合时。该项目将有助于确定抗磷脂疾病的生化原因，并改进其诊断，为研究人员、医生和患者带来更好的了解和诊断。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.