RHEUMATOID ARTHRITIS (RA) RELATED AUTOANTIBODIES

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 风湿性关节炎（RA）是一种影响关节的自身免疫性疾病，导致关节破坏、显著的发病率和增加的死亡率。对其他自身免疫性疾病的分析表明，大多数最终在临床上受到这些病症影响的个体表现出疾病进展的三个连续阶段：1）主要通过HLA关联携带遗传风险，2）存在临床沉默的自身抗体一年或多年，和3）临床上明显的靶器官损伤。 自身免疫性疾病演变的研究，其主要结局指标是无症状个体中的疾病相关自身免疫，而不是临床上明显的疾病本身，可以提供对发病机制的独特见解，因为它们是在没有实质性回忆偏倚或临床活动性疾病和靶器官损伤的不利影响的情况下完成的。 我们建议，RA也表现出这些阶段的疾病和遗传风险和自身抗体阳性，但临床上不受影响的个人内的流行病学协会的分析将提供重要的见解，这种疾病的发病机制。 为了解决这些问题，我们提出了一项研究，我们将招募一个人口的一级亲属（FDR）的个人与RA。 我们将利用该队列获得相关的遗传学和流行病学数据，并实现以下主要具体目标：具体目标#1：在RA个体的未受影响的FDR中，确定高危HLA等位基因的携带与RA相关自身抗体的存在之间的关联。 具体目标#2：在未受影响的FDR人群中，确定流行病学暴露与RA相关自身抗体存在之间的关系。

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.