Microarray-Based Biomarkers in Juvenile Idiopathic Arthritis

幼年特发性关节炎中基于微阵列的生物标志物

• 批准号: 8546146
• 负责人: JAMES N JARVIS
• 金额: $ 47.44万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8546146
• 关键词: Acute; Adult; Age; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Applications Grants; Area; Benchmarking; Biological; Biological Assay; Biological Markers; Biology; Caring; Child; Childhood; Chronic; Chronic Childhood Arthritis; Chronic Disease; Clinical; Clinical Trials; Complex; Computational Biology; Contracture; Cross-Sectional Studies; Crutches; Data; Data Set; Diagnosis; Discipline; Disease; Disease remission; Double-Blind Method; Equilibrium; Etanercept; Future; Gene Chips; Gene Expression; Gene Expression Profile; Genes; Goals; Inflammation; Joints; Laboratories; Learning; Longitudinal Studies; Marketing; Medicine; Methotrexate; Mind; Molecular; Molecular Profiling; Outcome; Parents; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Physiological Processes; Prednisone; Prospective Studies; Research; Research Design; Research Personnel; Rheumatoid Arthritis; Rheumatoid Factor; Rheumatology; Sampling; Splint Device; Surgical Intensive Care; TNF gene; Techniques; Technology; Testing; Therapeutic; Time; Training; Translating; Treatment Efficacy; United States National Institutes of Health; Wheelchairs; Whole Blood; Work; base; clinical application; clinical remission; cohort; communicable disease diagnosis; cost; data modeling; experience; genome-wide; high throughput technology; improved; inhibitor/antagonist; patient population; peripheral blood; prospective; public health relevance; response; screening; success; treatment response

DESCRIPTION (provided by applicant): We are entering an exciting era in pediatric rheumatology. New treatment approaches are improving the lives of children with juvenile idiopathic arthritis (JIA) to such a degree that it's now rare to see wheelchairs or crutches in our waiting rooms. Even splints, commonly used in the past to treat joint contractures, are seldom seen on our patients. Despite our progress, remission in JIA is rare. Recent work by our collaborator, Dr. Carol Wallace, has shown that only 5% of children with the polyarticular JIA (the most severe form of this disease) are in remission 5 years after diagnosis. Part of our problem in achieving remission is that, at the biological level, we don't really understand what "remission" is. It's a classic case of the difficulty of getting somewhere when you don't really know where you're trying to get. This grant application is about learning where we are trying to get. In this application, we aim to achieve a better understanding of what "remission" is using microarray-based biomarkers. Research from the Cobb (acute inflammation) and Jarvis (chronic inflammation) laboratories has demonstrated the feasibility of using genome-wide expression profiling can be used to define disease "states" (e.g., infected vs. not infected; in remission or not in remission). Furthermore, the Jarvis laboratory has demonstrated the promise of using these same technologies to predict clinical outcomes. For each group, these promising preliminary studies must be validated using larger patient populations and prospective study designs. In this application, we propose to validate peripheral blood biomarkers that already suggest that: (1) remission in juvenile arthritis can be identified at the molecular level through distinct gene expression signatures; (2) those signatures include the balance of both pro- and anti- inflammatory gene networks; and (3) the clinical course of children who reach an inactive disease state can be predicted based on molecular signatures that emerge in the peripheral blood mononuclear cells. Furthermore, we will take another step toward clinical application of this work by developing PCR-based whole blood assay to identify the most robust indicators of remission or clinical outcome. This project brings together two experienced investigators from two very different disciplines: pediatric rheumatology (Dr. Jarvis) and surgical intensive care (Dr. Cobb). Furthermore, the project brings together two computational biology groups spanning multiple disciplines, as well as other experienced pediatric rheumatology investigators. Thus, the project is highly responsive to the goals of the most recent NIH roadmap.

描述（由申请人提供）：