Gene Expression in Pediatric Arthritis

描述（由申请人提供）： 本计画计画资助金申请重点在于利用DNA微阵列（基因芯片）技术检测小儿关节炎患儿的基因差异表达。它建立在现有资源的基础上，并与申请人中心内现有的辛辛那提风湿病核心中心（P30）赠款提供强有力的互动和协同作用。生物技术的快速发展，包括人类基因组计划，包含人类基因组中几乎所有基因的高通量微阵列的出现，以及统计计算能力，共同创造了一个前所未有的机会，以完善诊断，治疗和理解儿科风湿性疾病的病理生理机制。提出了四个项目。Glass的项目专注于从多关节或少关节发作的幼年类风湿性关节炎（JRA）儿童的初始队列中识别外周血中疾病特异性基因表达谱。对这些患者的前瞻性随访将揭示基因表达模式如何随着疾病的演变和治疗而变化，并将提供对两种疾病亚型之间不同病理生理机制的见解。Hirsch的项目将对JRA滑膜进行全面的功能基因组分析，并阐明关节炎滑膜中成纤维细胞侵袭行为的分子途径。Colbert的项目专注于幼年脊柱关节病（JSpA），旨在确定表达谱是否将JSpA与其他形式的儿科关节炎和对照区分开来。Grom的项目将确定早期疾病的表达谱是否可以区分进展为侵袭性关节疾病的全身性JRA（sJRA）患者与未进展的患者，并确定疾病早期和晚期NK功能障碍的程度。此外，将sJRA急性巨噬细胞活化综合征（MAS）患者的表达模式与MAS消退后和有MAS病史的患者的表达模式进行比较。管理部门将与MCRC方法中心一起管理前瞻性临床研究，以确保适当收集和处理人口统计学和临床表型数据。行政单位还将提供领导和评估计划的进展。Tissue Core是P30 Tissue Repository的扩展，将处理从初始采集到发布到Affyandroid Core的生物样本。信息学Corelis建议与项目工作人员一起管理和分析数据，并开发一个网络支持的国家级基因组数据库。

DESCRIPTION (provided by applicant): This program project grant application focuses on the use of DNA micro array (gene chip) technology to detect differential expression of genes in children with pediatric arthritis. It builds on the existing resources and provides strong interactions and synergism with the Cincinnati Rheumatic Diseases Core Center (P30) grants in existence within the applicants' center. Rapid advances in biotechnology, including the human genome project, the advent of high through put micro arrays that contain nearly all genes in the human genome, and statistical computing power have come together to create an unprecedented opportunity to refine the diagnosis, treatment, and understanding of the pathophysiologic mechanisms involved in pediatric rheumatic diseases. Four projects are proposed. Project by Glass focuses on the recognition of disease specific gene expression profiles in peripheral blood from inception cohorts of children with either poly or pauciarticular onset juvenile rheumatoid arthritis (JRA). Prospective follow-up of these patients will reveal how gene expression patterns change with disease evolution and therapy and will provide insights into varying pathophysiological mechanisms between the two disease subtypes. Project by Hirsch will perform a comprehensive functional genomic analysis of synovium in JRA, and elucidate the molecular pathways responsible for the aggressive behavior of fibroblasts in arthritic synovium. Project by Colbert focuses on juvenile spondyloarthropathies (JSpA) and aims to determine whether expression profiles distinguish JSpA from other forms of pediatric arthritis and controls. Project by Grom will determine if expression profiles in early disease can distinguish patients with systemic JRA (sJRA) who progress to an aggressive form of articular disease from those that do not, and determine the extent of NK dysfunction early and late in the disease. In addition, expression patterns among patients with sJRA who have acute macrophage activation syndrome (MAS) will be compared to patterns obtained after resolution of MAS and among those with a history of MAS. An Administrative Unit will in conjunction with the MCRC Methods Core manage the prospective clinical studies will assure proper collection and processing of demographic and clinical phenotype data. The Administrative Unit will also provide leadership and evaluate program progress. The Tissue Core, an extension of the P30 Tissue Repository will handle biological specimens from initial acquisition through to the release to the Affymetrix Core. An Informatics Corelis proposed to manage and analyze the data in conjunction with project staff and develop a web-enabled national level genomic database.