Proteomic Profiles and Novel Biomarkers in Juvenile Rheumatoid Arthritis

描述：(申请人提供)：幼年型类风湿性关节炎(JRA)包括一组不同的儿童期发病的慢性自身免疫性疾病，具有不同的临床表现、结果和治疗反应。虽然临床评估一直是确定可能的诊断和结果的中心和重要方法，但几乎没有实验室测试方法来帮助儿科风湿病医生对患者进行初步评估。人类基因组测序和分子技术的进步为揭开疾病过程提供了一个框架。基因表达分析是实现这一目标的一种方法，但直接介导疾病的是蛋白质，而不是RNA。因此，蛋白质表达可能比RNA表达提供更好的病理生理途径指标。蛋白质组学领域，或蛋白质模式分析，是对组织和体液中蛋白质的表征和定量。疾病蛋白质组学已经成为一门快速发展的学科，用于描述改变的蛋白质表达，识别用于疾病诊断和早期检测的新的生物标记物，以及识别新的治疗靶点。在第一个具体目标中，我们将结合使用表面增强激光解吸/电离飞行时间质谱仪(SELDI-TOF-MS)、Cliniprot和二维凝胶分析来描绘外周血和关节液中差异蛋白的表达，以区分疾病状态和JRA亚型。然后，第二个特定目标建议识别这些差异表达的蛋白质，并将它们与JRA的疾病状态和亚型相关联。这项研究的总体目标将是全面识别可能参与JRA致病途径的蛋白质组图谱和差异表达的蛋白质。它可能会导致对疾病机制的更多了解，并可能作为疾病的诊断和预后指标。此外，这些研究可能导致识别新的生物标记物和治疗JRA的靶点。

DESCRIPTION: (provided by applicant): Juvenile Rheumatoid Arthritis (JRA) comprises a heterogeneous group of childhood onset, chronic, autoimmune diseases with variable clinical presentations, outcomes and therapeutic responses. Little is available by way of laboratory testing to help the pediatric rheumatologist in the initial evaluation of patients although clinical evaluation has been a central and important method of establishing likely diagnoses and outcomes. The sequencing of the human genome and advances in molecular technologies has provided a framework to unravel disease processes. Gene expression analysis is one approach to achieving this end, but it is protein, rather than RNA, that directly mediates disease. Thus, protein expression is likely to provide a better indicator of pathophysiologic pathways than does RNA expression. The field of proteomics, or protein pattern analysis, is the characterization and quantitation of proteins in tissues and body fluids. Disease proteomics has emerged as a rapidly advancing discipline for delineating altered protein expression, identifying novel biomarkers for the diagnosis and early detection of disease, and the identification of new targets for therapeutics. In the first specific aim, we will use a combination of Surface Enhanced Laser Desorption/lonization time of flight mass spectrometry (SELDI-TOF-MS), Cliniprot, and 2-dimensional gel analysis for delineating differential protein expression in peripheral blood and joint fluids to differentiate disease states and between subtypes of JRA. The second specific aim then proposes to identify these differentially expressed proteins and correlate them with the disease state and subtype of JRA. The overall goal of the studies will be to comprehensively identify proteomic profiles and differentially expressed proteins which are likely to be involved in pathogenic pathways in JRA. It will likely lead to greater understanding of the mechanism of disease as well as potentially serve as diagnostic and prognostic indicators of disease. Furthermore, these studies may lead to the identification of novel biomarkers and targets of therapy in JRA.