Predictors of Rheumatoid Arthritis (RA) Severity in African Americans

非裔美国人类风湿性关节炎 (RA) 严重程度的预测因素

• 批准号: 8304148
• 负责人: S Louis Bridges
• 金额: $ 25.65万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304148
• 关键词: Affect; African American; Alleles; Anti-citrullinated peptide antibody; Autoimmune Process; Biological Assay; Biological Markers; Biotechnology; Caucasians; Caucasoid Race; Clinical; Clinical Research; Collaborations; Complex; Crohn' s disease; DNA; Data; Disease; Disease susceptibility; Enrollment; Environmental Risk Factor; Epitopes; Ethnic Origin; Evaluation; Funding; Gene Expression; Gene Expression Profiling; Genetic; Genome; Genomics; Goals; Growth Factor; Individual; Inflammatory; Interferons; Knowledge; Laboratories; Longitudinal Studies; Methodology; Minor; Molecular; Molecular Profiling; Morbidity - disease rate; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Outcome; PTPN22 gene; Pathogenesis; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Physicians; Predisposition; Prospective Studies; Proteomics; Quality of life; RNA; Race; Relative (related person); Research Personnel; Rheumatoid Arthritis; Rheumatoid Factor; Rheumatology; Risk; Sampling; Serological; Serum; Serum Proteins; Severities; Severity of illness; Signal Pathway; Single Nucleotide Polymorphism; Societies; Socioeconomic Status; Statistical Models; Stratification; Systemic Lupus Erythematosus; Techniques; Testing; Translating; Treatment Cost; United States National Institutes of Health; arthritis registry; base; clinical care; cost; cytokine; genome-wide; high risk; human disease; illness length; improved; insight; joint injury; multidisciplinary; non-genetic; prospective; protein profiling; receptor; research study; socioeconomics; treatment strategy

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.

早期类风湿患者分层的遗传、血清和临床因素鉴定 根据放射学严重程度的风险，关节炎（RA）将改善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。遗传对X线检查的影响 RA的严重程度可能因种族/民族而异，非洲裔美国人在RA中的代表性明显不足 调查研究。全基因组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的标志物的方法。我们假设 PBMCs中的基因表达模式、血清蛋白质谱和临床参数可以成功地 区分患有早期RA的非洲裔美国人，他们将发展严重的放射学损伤， 不会的美国国立卫生研究院资助的CLEAR（非裔美国人早期 RA）登记研究是一项独特的多中心、前瞻性、纵向研究， 可以获得社会经济、临床和连续放射学数据，以及DNA和血清。通过 与自身免疫生物标志物合作网络（ABCoN）合作，RNA样本适合于 基因表达微阵列分析目前是在CLEAR患者上进行的。我们提议下列 具体目标：1.确定非裔美国人PBMCs基线基因表达谱的差异 使用微阵列，在3年的疾病持续时间中具有重度与轻度放射学损伤的RA患者; 2.到 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 使用基于芯片和珠粒的方法测定一组细胞因子、生长因子和可溶性受体的血清水平 分析;和3.确定临床、遗传和血清学因素对 使用MCRC方法学开发的统计模型评估非裔美国人RA的放射学严重程度 核心该提案的最终目标是将临床流变学、生物技术、 和统计遗传学的临床有用的测试，以预测在非洲裔美国人的类风湿关节炎的放射严重程度。 当建立了可靠的放射学严重程度标志物时，可以优化治疗策略 这将显著改善非裔美国人类风湿关节炎患者的临床护理。在 此外，这些研究将为RA的发病机制提供相当多的新见解。