RHEUMATOID ARTHRITIS (RA) RELATED AUTOANTIBODIES

类风湿性关节炎 (RA) 相关自身抗体

• 批准号: 7951915
• 负责人: PETER K. GREGERSEN
• 金额: $ 0.59万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951915
• 关键词: Address; Affect; Alleles; Autoantibodies; Autoimmune Diseases; Autoimmunity; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Disease; Disease Progression; Evolution; Exhibits; First Degree Relative; Funding; Genetic; Genetic Risk; Grant; Individual; Injury; Institution; Joints; Morbidity - disease rate; Organ; Outcome Measure; Pathogenesis; Phase; Population; Recruitment Activity; Research; Research Personnel; Resources; Rheumatoid Arthritis; Risk; Source; United States National Institutes of Health; cohort; epidemiologic data; high risk; insight; joint destruction; mortality; primary outcome

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rheumatoid Arthritis (RA) is an autoimmune disease that affects joints, leading to joint destruction, significant morbidity and increased mortality. Analysis of other autoimmune diseases has shown that the majority of individuals that are ultimately clinically affected with these conditions exhibit three sequential phases of disease progression: 1) Carriage of genetic risk primarily through HLA associations, 2) Presence of clinically silent autoantibodies for one or more years, and 3) Clinically apparent target organ injury. Studies of autoimmune disease evolution whose primary outcome measures are disease-related autoimmunity in asymptomatic individuals, rather than clinically apparent disease itself, can provide unique insights into pathogenesis because they are accomplished without substantial recall bias or the untoward effects of clinically active disease and target organ damage. We propose that RA also exhibits these phases of disease and that analysis of epidemiologic associations within the genetically at-risk and autoantibody positive but clinically unaffected individuals will provide important insights into the pathogenesis of this disease. To address these issues, we propose a study in which we will recruit a population of first degree relatives (FDR) of individuals with RA. We will utilize this cohort to obtain relevant genetic and epidemiologic data and accomplish the following primary specific aims: Specific Aim #1: In unaffected FDRs of individuals with RA, determine the association between the carriage of high risk HLA alleles and the presence of RA-related autoantibodies. Specific Aim #2: In this population of unaffected FDRs, determine the association between epidemiologic exposures and the presence of RA-related autoantibodies.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 类风湿关节炎（RA）是一种自身免疫性疾病，会影响关节，导致关节破坏，明显的发病率和死亡率增加。对其他自身免疫性疾病的分析表明，大多数最终受这些疾病临床影响的个体表现出疾病进展的三个顺序阶段：1）主要通过HLA关联运输遗传风险，主要通过HLA关联，主要是存在临床上静止的自身抗体一年或多年，以及3）临床明显的目标器官损伤。 对自身免疫性疾病进化的研究，其主要结局指标是无症状的个体中与疾病相关的自身免疫性，而不是临床明显的疾病本身，可以为发病机理提供独特的见解，因为它们是没有实质性回忆偏见或临床上活性疾病和目标器官损害的不良影响而实现的。 我们建议RA还表现出这些疾病的这些阶段，并分析遗传性高危和自身抗体阳性的流行病学关联，但临床上未受影响的个体将为这种疾病的发病机理提供重要的见解。 为了解决这些问题，我们提出了一项研究，其中我们将招募有RA患者的一级亲戚（FDR）。 我们将利用此队列来获得相关的遗传和流行病学数据，并完成以下主要特定目的：特定目的＃1：在没有RA的个体的FDR中，确定了高风险HLA等位基因的运输与存在RA相关自身抗体的相关性。 具体目的＃2：在未受影响的FDR人群中，确定流行病学暴露与RA相关自身抗体的存在之间的关联。