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.

鉴定遗传，血清和临床因素，以允许早期类风湿的患者分层 关节炎（RA）根据射线照相严重程度的风险将改善RA患者的生活质量， 通过大大降低发病率和治疗成本来使社会受益。遗传对射线照相的影响 RA的严重性可能因种族/种族而异，非裔美国人在RA中的代表性不足 研究。全基因组基因表达分析和蛋白质组学技术已经革新 识别疾病易感性和严重性标记的方法。我们假设一个组合 PBMC，血清蛋白谱和临床参数中的基因表达模式可以成功 与早期RA的非裔美国人区分开，他们将对那些人造成严重的射线照相损害 不会。 NIH资助的明确（用于对非裔美国人进行纵向评估的财团 RA）注册表是一项独特的多中心，前瞻性，纵向研究，其中全面的人口统计学， 可以使用社会经济，临床和串行射线照相数据以及DNA和血清。通过 与适用于RNA样本的自动免疫生物标志物协作网络（ABCON）合作 目前，基因表达微阵列分析是对清晰的患者进行的。我们提出以下内容 具体目的：1。确定非裔美国人PBMC中基线基因表达谱的差异 使用微阵列，在3年疾病持续时间的RA患者与轻度射线照相损伤的患者； 2 通过分析基线来确定影响非裔美国人RA的射线照相严重程度的血清学因素 使用芯片和基于珠的细胞因子，生长因子和可溶性受体的血清水平 测定； 3。确定临床，遗传和血清学因素对 使用MCRC Methology开发的统计模型在非裔美国人中RA的影像学严重程度 核。该提案的最终目标是转化临床风湿病学，生物技术，生物技术的见解 和统计遗传学进入临床上有用的测试，以预测非裔美国人RA的射线照相严重程度。 当建立可靠的放射学严重程度的可靠标记时，可以优化治疗状态 对于个别患者，这将显着改善具有RA的非裔美国人的临床护理。在 此外，这些研究将为RA的发病机理提供大量的新见解。