High Throughput Screening of the Autoimmune Epitome

描述（由申请人提供）：本申请涉及广泛的挑战领域（04）临床研究和特定的挑战主题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）的影响。这些疾病造成相当高的发病率和死亡率，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，需要多次拜访医学专家，并解释不完美的测试。即使诊断是确定的，提供预后或个性化治疗的工具也往往缺乏。该项目的总体目标是快速和彻底地评估一种用于测量SLE特异性抗体的新技术，SLE是系统性自身免疫模型。该技术基于称为“类肽”的N-取代甘氨酸的合成聚合物作为免疫球蛋白的特异性配体的能力。将进行两个具体目标：1）使用系统性红斑狼疮作为模型验证IgG生物标志物发现的新技术平台，以及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，高度特异性的类肽配体将被合成、纯化并连接到荧光珠上以创建高通量筛选平台。然后，它们将用于测量和表征来自具有临床明显SLE的受试者以及具有早期或不完全形式的疾病的受试者的自身抗体。总之，这项研究的结果将导致临床医生和临床研究人员在评估自身免疫性疾病中使用的新工具的开发。 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。利用这一模型系统，希望其他自身免疫性疾病将受益于早期诊断和治疗。

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.