High Throughput Screening of the Autoimmune Epitome

描述(申请人提供)：本申请涉及广泛的挑战领域(04)临床研究和特定挑战主题04-AR-101皮肤、关节、肌肉和其他组织疾病的自身免疫。据估计，大约5%的美国人口受到自身免疫性疾病的影响，如类风湿性关节炎(RA)、系统性红斑狼疮(SLE)或多发性硬化症(MS)。这些疾病导致相当大的发病率和超额死亡率，以及数百亿美元的直接和间接保健费用。这些疾病的诊断往往很困难，需要多次去看医学专家，并对不完美的测试进行解释。即使诊断是肯定的，提供预后或个性化治疗的工具往往也是缺乏的。这个项目的总体目标是快速和彻底地评估一种新的技术，用于测量系统性自身免疫的模型SLE的特异性抗体。这项技术是基于N-取代甘氨酸的合成聚合物作为免疫球蛋白的特定配体的能力。将进行两个具体目标：1)以系统性红斑狼疮为模型，验证新的免疫球蛋白生物标记物发现技术平台；2)确定类肽配体识别临床前自身免疫的能力。为了实现这些目标，将合成、纯化并连接到荧光小球上的高度特异性的类肽配体，以创建一个高通量的筛选平台。然后，它们将被用于测量和表征临床明显的SLE患者以及早期或不完全SLE患者的自身抗体。总而言之，这项研究的结果将导致临床医生和临床研究人员开发新的工具，用于评估自身免疫性疾病。 公共卫生相关性：自身免疫性疾病是难以诊断和监测的常见疾病原因。这项研究将测试一种全新的方法来监测系统性红斑狼疮患者血液成分的变化。以此为模式系统，希望其他自身免疫性疾病也能从早期诊断和治疗中受益。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (04) Clinical Research and specific Challenge Topic 04-AR-101 Autoimmunity for Diseases of Skin, Joints, Muscles and Other Tissues. It is estimated that approximately 5% of the US population is affected by an autoimmune disorder such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or multiple sclerosis (MS). These conditions cause considerable morbidity and excess mortality, as well as direct and indirect health care costs in the tens of billions of dollars. The diagnosis of these conditions is often difficult, requiring multiple visits to medical specialists, and the interpretation of imperfect tests. Even when the diagnosis is certain, the tools to offer prognosis or personalize therapy are often lacking. The overall goal of this project is to rapidly and thoroughly evaluate a novel technology for the measurement of antibodies specific for SLE, a model for systemic autoimmunity. The technology is based on the ability of synthetic polymers of N-substituted glycine termed 'peptoids' to serve as specific ligands for immunoglobulin. Two specific aims will be undertaken: 1) Validation of a novel technology platform for IgG biomarker discovery using systemic lupus erythematosus as a model, and 2) Determine the ability of peptoid ligands to identify pre-clinical autoimmunity. To accomplish these aims, highly specific peptoid ligands will be synthesized, purified and attached to fluorescent beads to create a high-throughput screening platform. They will then be used to measure and characterize autoantibodies from subjects with clinically evident SLE as well as those with early or incomplete forms of the disease. Together, the results of this study will lead to the development of new tools for clinicians and clinical researchers to use in the assessment of autoimmune diseases. PUBLIC HEALTH RELEVANCE: Autoimmune diseases are common causes of illness that are difficult to diagnose and monitor. This study will test a completely new method to monitor changes in the composition of the blood of patients with systemic lupus erythematosus. Using this as a model system, it is hoped that other autoimmune diseases will benefit from early diagnosis and treatment.