Causes and Roles of Hypercitrullination in Preclinical Rheumatoid Arthritis

临床前类风湿性关节炎中瓜氨酸过度化的原因和作用

• 批准号: 10218058
• 负责人: I-CHENG HO
• 金额: $ 39.51万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218058
• 关键词: Affect; Aftercare; Antibodies; Antirheumatic Agents; Arginine; Arginine deiminase; Attenuated; Biochemical; Blood Cells; CD3 Antigens; Caring; Cells; Chronology; Citrulline; Clinical; Data; Deltastab; Disease; Early Diagnosis; Environment; Event; Exhibits; Family; First Degree Relative; General Population; Genes; Genetic Variation; Goals; Harvest; Histone H3; Immune; Impairment; Inflammation; Interruption; Light; Longitudinal cohort study; Mediating; Molecular; Motion; Newly Diagnosed; North America; PTPN22 gene; Participant; Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Pharmacology; Phenotype; Phosphoric Monoester Hydrolases; Post-Translational Protein Processing; Prevention; Process; RNA; Recording of previous events; Rheumatoid Arthritis; Role; Serum; Shapes; Symptoms; Testing; TimeLine; Whole Blood; citrullinated protein; clinical development; cohort; effective therapy; genetic approach; high risk; immune function; pre-clinical; preclinical study; response

Project Summary Rheumatoid arthritis (RA) affects up to 1-2% of the general population in North America. The cause of RA is still not fully understood but involves complicate interactions between genes and environment. As more effective therapies for RA are emerging, the focus of RA care is shifting from controlling inflammation to early detection, prevention, and cure of this disease. The ultimate goal of this project is to understand how the disease process of RA is initiated. Preliminary data of this study suggest that blood cells obtained from healthy first-degree relatives (FDRs) of RA patients already display several abnormal features that are also seen in untreated RA patients, indicating that those abnormal features predate the clinical symptoms of RA. The first aim of this project is to use biochemical approaches to characterize those abnormal features in blood cells from FDRs, and to establish a chronological and causal relationship among those features. The second aim is to use pharmacological and genetic approaches to examine how the cascade of the abnormal features is triggered and how one feature leads to the next. The final aim is to examining blood cells obtained from newly diagnosed RA patients before and after treatments in order to determine if effective RA treatment will mitigate these abnormal features. Taken together, this project will delineate a sequence of molecular events leading to the development of clinical symptoms of RA and will bring us one step closer to the initial trigger of RA.

项目摘要 类风湿关节炎（RA）影响北美多达1-2％的普通人群。 RA的原因是 仍然没有完全理解，但涉及基因与环境之间的复杂相互作用。更多 有效的RA疗法正在出现，RA护理的重点正在从控制炎症转变为早期 该疾病的检测，预防和治愈。该项目的最终目标是了解 启动RA的疾病过程。这项研究的初步数据表明，从健康获得的血细胞 RA患者的一级亲戚（FDR）已经显示出几种异常特征 未经治疗的RA患者，表明这些异常特征早于RA的临床症状。第一个 该项目的目的是使用生化方法来表征血细胞中这些异常特征 来自FDR，并在这些特征之间建立时间顺序和因果关系。第二个目标是 使用药理和遗传方法来检查异常特征的级联 触发以及一个功能如何导致下一个功能。最终目的是检查从新近获得的血细胞 诊断为治疗前后的RA患者，以确定有效的RA治疗是否会减轻 这些异常特征。综上所述，该项目将描述一系列分子事件，导致 RA的临床症状的发展，将使我们更接近RA的初始触发。