Gene Expression in Pediatric Arthritis

小儿关节炎中的基因表达

• 批准号: 6795438
• 负责人: DAVID N. GLASS
• 金额: $ 141.9万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-22 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6795438
• 关键词: children; clinical research; disease /disorder classification; functional /structural genomics; gene expression; human subject; juvenile rheumatoid arthritis; microarray technology; molecular pathology; patient oriented research

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.

描述（由申请人提供）： 该计划项目资助申请的重点是利用DNA微阵列（基因芯片）技术检测小儿关节炎患儿基因的差异表达。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) 拨款提供强有力的互动和协同作用。生物技术的快速进步，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，共同创造了前所未有的机会，以完善儿科风湿性疾病的诊断、治疗和病理生理机制的理解。提出了四个项目。 Glass 的项目重点是识别多发或少关节型幼年类风湿性关节炎 (JRA) 儿童初始队列的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，并阐明导致关节炎滑膜中成纤维细胞侵袭行为的分子途径。 Colbert 的项目重点关注青少年脊柱关节病 (JSpA)，旨在确定表达谱是否能将 JSpA 与其他形式的小儿关节炎和对照区分开来。 Grom 的项目将确定早期疾病中的表达谱是否可以区分患有侵袭性关节疾病的全身性 JRA (sJRA) 患者与未进展为侵袭性关节疾病的患者，并确定疾病早期和晚期 NK 功能障碍的程度。此外，患有急性巨噬细胞活化综合征（MAS）的 sJRA 患者的表达模式将与 MAS 消退后以及有 MAS 病史的患者中获得的模式进行比较。行政单位将与 MCRC 方法核心一起管理前瞻性临床研究，以确保人口统计和临床表型数据的正确收集和处理。行政部门还将提供领导并评估计划进展。 Tissue Core 是 P30 组织存储库的扩展，将处理从最初采集到释放到 Affymetrix Core 的生物样本。信息学 Corelis 建议与项目人员一起管理和分析数据，并开发一个支持网络的国家级基因组数据库。