Predictors of Rheumatoid Arthritis (RA) Severity in African Americans

确定遗传、血清和临床因素，以便对早期类风湿患者进行分层 根据放射学严重程度的风险进行关节炎(RA)可以改善RA患者的生活质量， 通过大幅降低发病率和治疗成本，造福社会。遗传因素对射线照相的影响 类风湿关节炎的严重程度可能因种族/民族而异，非裔美国人在类风湿关节炎中的代表性明显不足 研究性研究。全基因组的基因表达谱和蛋白质组学技术已经彻底改变了 确定疾病易感性和严重性标记物的方法。我们假设一种组合 外周血单核细胞的基因表达模式、血清蛋白谱和临床参数的研究可以成功 将患有早期类风湿性关节炎的非洲裔美国人与那些 不会的。NIH资助的Clear(早期非裔美国人纵向评估联盟 RA)登记是一项独特的多中心、前瞻性、纵向研究，在这项研究中， 社会经济、临床和系列放射数据，以及DNA和血清，都是可用的。穿过 与自身免疫生物标记物合作网络(ABCON)合作，RNA样本适用于 基因表达微阵列分析目前是建立在明确的患者身上的。我们提出以下建议 具体目的：1.确定非裔美国人外周血单核细胞基线基因表达谱的差异 使用微阵列技术对病程3年的RA患者进行放射学检查：严重损害与轻度损害； 通过分析基线确定影响非裔美国人RA放射学严重程度的血清学因素 应用芯片和微珠技术检测一组细胞因子、生长因子和可溶性受体的血清水平 检测；以及3.确定临床、遗传和血清因素对 应用MCRC方法学开发的统计模型研究非裔美国人类风湿关节炎的放射学严重程度 核心。这项建议的最终目标是将临床风湿学、生物技术、 和统计遗传学转化为临床有用的测试，以预测非裔美国人类风湿关节炎的放射学严重程度。 当建立了稳健、可靠的放射学严重程度的标记时，可以优化治疗策略 对于个别患者，这将显著改善非裔美国人RA的临床护理。在……里面 此外，这些研究将为类风湿关节炎的发病机制提供相当多的新见解。

Identification of genetic, serum, and clinical factors to allow stratification of patients with early rheumatoid arthritis (RA) according to risk of radiographic severity would improve quality of life for RA patients and benefit society by substantially lowering morbidity and treatment costs. Genetic influences on radiographic severity of RA may vary by race/ethnicity, and African-Americans are significantly under-represented in RA research studies. Genome-wide gene expression profiling and proteomic techniques have revolutionized approaches to identifying markers of disease susceptibility and severity. We hypothesize that a combination of gene expression patterns in PBMCs, serum protein profiles, and clinical parameters can successfully distinguish African-Americans with early RA who will develop severe radiographic damage from those who will not. The NIH-funded CLEAR (Consortium for the Longitudinal Evaluation of African-Americans with Early RA) Registry is a unique multi-center, prospective, longitudinal study in which comprehensive demographic, socioeconomic, clinical, and serial radiographic data, as well as DNA and serum, are available. Through collaboration with the Autoimmune Biomarkers Collaborative Network (ABCoN), RNA samples suitable for gene expression microarray analyses are currently banked on CLEAR patients. We propose the following specific aims: 1. To identify differences in baseline gene expression profiles in PBMCs of African-American RA patients with severe vs. mild radiographic damage at 3 years' disease duration, using microarrays; 2. To identify serologic factors influencing radiographic severity of RA in African-Americans by analyzing baseline serum levels of a panel of cytokines, growth factors, and soluble receptors using chip and bead-based assays; and 3. To determine the relative contributions of clinical, genetic, and serologic factors on radiographic severity of RA in African-Americans using statistical models developed by the MCRC Methology Core. The ultimate goal of this proposal is to translate insights from clinical rheumatology, biotechnology, and statistical genetics into clinically useful tests to predict radiographic severity of RA in African-Americans. When robust, reliable markers of radiographic severity are established, treatment stategies can be optimized for individual patients, which will significantly improve the clinical care of African-Americans with RA. In addition, these studies will provide considerable new insights into the pathogenesis of RA.