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）： 我们正在进入小儿风湿病学时代。新的治疗方法正在改善少年特发性关节炎（JIA）儿童的生活，以至于现在很少在我们的候诊室看到轮椅或拐杖。即使是过去通常用于治疗关节染色的夹板，我们的患者也很少看到。 尽管取得了进展，但JIA的缓解很少。我们的合作者Carol Wallace博士最近的工作表明，只有5％的聚会JIA儿童（这种疾病的最严重形式）在诊断后5年处于缓解状态。解决缓解方面的问题的一部分是，在生物学层面，我们并不真正了解“缓解”是什么。这是一个经典的案例，即当您真的不知道自己想获得的地方时难以到达某个地方。该赠款应用程序是关于学习我们要获得的位置。 在此应用程序中，我们旨在更好地了解使用基于微阵列的生物标志物的“缓解”。 COBB（急性炎症）和JARVIS（慢性炎症）实验室的研究表明，使用全基因组表达谱分析的可行性可用于定义疾病“状态”（例如，感染与未感染；在缓解中是否受到感染；此外，Jarvis实验室已经证明了使用这些相同技术预测临床结果的希望。对于每个组，必须使用较大的患者人群和前瞻性研究设计来验证这些有希望的初步研究。 在此应用中，我们建议验证外周血生物标志物已经表明：（1）可以通过不同的基因表达特征在分子水平上鉴定出少年关节炎的缓解； （2）这些特征包括促炎和抗炎基因网络的平衡； （3）可以根据外周血单核细胞中出现的分子特征来预测达到无活跃疾病状态的儿童的临床过程。此外，我们将通过开发基于PCR的全血分析来确定最强大的缓解或临床结果指标，迈出这项工作的临床应用又一步。 该项目汇集了来自两个非常不同学科的两名经验丰富的研究人员：小儿风湿病学（Jarvis博士）和外科重症监护（Cobb博士）。此外，该项目汇集了两个跨越多个学科的计算生物学组，以及其他经验丰富的小儿风湿病学研究者。因此，该项目对最近的NIH路线图的目标高度敏感。