RHEUMATOID ARTHRITIS (RA) RELATED AUTOANTIBODIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 类风湿性关节炎(RA)是一种影响关节的自身免疫性疾病，可导致关节破坏、严重发病率和死亡率增加。对其他自身免疫性疾病的分析表明，大多数最终在临床上受到这些疾病影响的个体表现出疾病发展的三个连续阶段：1)主要通过人类白细胞抗原相关携带遗传风险，2)临床上无症状的自身抗体存在一年或多年，以及3)临床上明显的靶器官损伤。对自身免疫性疾病演变的研究，其主要结果衡量的是无症状个体的疾病相关自身免疫，而不是临床上明显的疾病本身，可以为发病机制提供独特的见解，因为这些研究完成时没有实质性的回忆偏差或临床活动性疾病和靶器官损害的不良影响。 我们认为RA也表现出这些疾病的阶段，分析遗传高危和自身抗体阳性但临床未受影响的个体之间的流行病学联系将为这种疾病的发病机制提供重要的见解。 为了解决这些问题，我们提出了一项研究，在这项研究中，我们将招募RA患者的一级亲属(FDR)。我们将利用这个队列来获得相关的遗传和流行病学数据，并实现以下主要的特定目标：特定目标1：在RA患者的未受影响的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联。

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.