Use of Microarrays to Understand Systemic Arthritis

使用微阵列了解系统性关节炎

• 批准号: 7117281
• 负责人: Maria Virginia Pascual
• 金额: $ 31.75万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-22 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7117281
• 关键词: adolescence (12-20); cellular pathology; child (0-11); chronic disease /disorder; clinical research; communicable diseases; disease /therapy duration; epidemiology; gene expression; gene mutation; genetic mapping; human subject; immunity; immunogenetics; immunoregulation; infectious arthritis; juvenile rheumatoid arthritis; leukocytes; microarray technology; pathologic process; patient oriented research; prognosis

DESCRIPTION (provided by applicant): Systemic Onset Juvenile Chronic Arthritis (SOJCA) is a disease that carries severe long-term disability for 50% of the children who suffer from it. The pathogenesis of this disease remains a mystery and there are no animal models to reproduce it. As opposed to other forms of Juvenile Chronic Arthritis, no serologic markers like autoantibodies, HLA associations, or other specific diagnostic tests are available. We now have preliminary data showing significant alterations in the blood mononuclear cells from SOJCA patients, including 1) increased numbers of blood monocytes with an activated phenotype, 2) a gene signature shared with patients with bacterial infections, 3) a unique gene signature. The present proposal aims at further strengthening these data through the accrual of a larger number of patients and the analyses of a larger selection of genes. We expect that these studies will provide us with clues to understand the pathogenesis of the disease. We are particularly intrigued by the similarities observed between SOJCA and systemic infections especially with those caused by Staphylococcus aureus. We propose to correlate the SOJCA genetic signature with the outcome of the disease. In particular, the four-year proposed study will permit us to compare the gene profiles of patients who get disease resolution from those who develop a chronic, highly debilitating disease. In vitro studies are designed to eventually identify the cellular and molecular mechanisms leading to the SOJCA signature, thereby allowing us to better understand the disease. Our ultimate goal is to design novel therapies to antagonize the causative agent and/or the genetic pathways responsible for the establishment of this intriguing disease.

描述（由申请人提供）： 全身性发作少年慢性关节炎（SOJCA）是一种疾病，可为50％的患有疾病的儿童带来严重的长期残疾。这种疾病的发病机理仍然是一个谜，没有动物模型可以繁殖它。与其他形式的少年慢性关节炎相反，没有血清学标记（例如自身抗体，HLA关联或其他特定的诊断测试）。现在，我们拥有初步数据，显示了来自SOJCA患者血液单核细胞的显着改变，包括1）具有活化表型的血液单核细胞数量增加，2）与细菌感染患者共享的基因签名，3）独特的基因签名。本提案旨在通过大量患者的应计和较大基因选择的分析来进一步加强这些数据。我们预计这些研究将为我们提供了解该疾病发病机理的线索。我们对sojca和全身感染之间的相似性特别感兴趣，尤其是金黄色葡萄球菌引起的相似之处。我们建议将SOJCA遗传特征与疾病的结果相关联。特别是，这项为期四年的研究将使我们能够比较从患有慢性，高度衰弱的疾病的患者中得到疾病解决的患者的基因谱。体外研究旨在最终确定导致SOJCA特征的细胞和分子机制，从而使我们能够更好地理解该疾病。我们的最终目标是设计新型疗法，以拮抗导致这种有趣疾病的原因的病因和/或遗传途径。