Proteomic Profiles and Novel Biomarkers in Juvenile Rheumatoid Arthritis

幼年类风湿关节炎的蛋白质组谱和新型生物标志物

• 批准号: 7631477
• 负责人: MARGALIT E ROSENKRANZ
• 金额: $ 19.82万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-22 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7631477
• 关键词: Acute-Phase Proteins; Adverse effects; Arthritis; Autoimmune Process; Biological Markers; Body Fluids; Child; Childhood; Chronic; Chronic Childhood Arthritis; Clinical; Data; Development; Diagnosis; Diagnostic; Discipline; Disease; Early Diagnosis; Evaluation; Functional disorder; Gel; Gene Expression; Genetic Transcription; Goals; Haptoglobins; Human Genome; Inflammatory; Joints; Laboratories; Lasers; Lead; Liquid substance; Mass Spectrum Analysis; Mediating; Methods; Molecular; Molecular Profiling; Outcome; Pathogenesis; Pathway interactions; Patient Care; Patients; Pattern; Process; Proteins; Proteomics; Research Personnel; Rheumatology; Risk; Serum; Serum amyloid A protein; Surface; Synovial Fluid; Techniques; Technology; Testing; Therapeutic; Time; aggressive therapy; chronic autoimmune disease; disorder control; gel electrophoresis; improved; new therapeutic target; novel; peripheral blood; prevent; prognostic; prognostic indicator; programs; protein expression; research clinical testing; response; rheumatologist; two-dimensional

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.

产品说明：（申请人提供）：幼年型风湿性关节炎（JRA）包括一组异质性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。虽然临床评估是确定可能的诊断和结果的中心和重要方法，但通过实验室检测来帮助儿科风湿病学家对患者进行初步评估的方法很少。人类基因组测序和分子技术的进步为揭示疾病过程提供了框架。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学途径的指标。蛋白质组学或蛋白质模式分析的领域是组织和体液中蛋白质的表征和定量。 疾病蛋白质组学已成为一门快速发展的学科，用于描绘改变的蛋白质表达，鉴定用于疾病诊断和早期检测的新生物标志物，以及鉴定用于治疗的新靶点。在第一个具体目标中，我们将使用表面增强激光解吸/电离飞行时间质谱（SELDI-TOF-MS）、Cliniprot和二维凝胶分析的组合来描绘外周血和关节液中的差异蛋白表达，以区分疾病状态和JRA亚型。第二个具体目标，然后提出，以确定这些差异表达的蛋白质，并将它们与疾病状态和亚型的JRA。 研究的总体目标是全面鉴定可能参与JRA致病途径的蛋白质组学谱和差异表达蛋白。它可能会导致更好地了解疾病的机制，并可能作为疾病的诊断和预后指标。此外，这些研究可能会导致新的生物标志物和治疗JRA的目标的识别。