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: 9980794
• 负责人: I-CHENG HO
• 金额: $ 40.74万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980794
• 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.

项目概要 类风湿性关节炎 (RA) 影响北美普通人群的 1-2%。 RA的病因是 仍未完全理解，但涉及基因与环境之间复杂的相互作用。随着更多 RA 的有效治疗方法不断涌现，RA 护理的重点正从控制炎症转向早期治疗 检测、预防和治疗这种疾病。该项目的最终目标是了解如何 RA的疾病进程开始。这项研究的初步数据表明，从健康人身上获得的血细胞 RA 患者的一级亲属 (FDR) 已经表现出一些异常特征，这些特征也出现在 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 该项目的目的是利用生化方法来表征血细胞中的异常特征 从 FDR 中提取数据，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 使用药理学和遗传学方法来检查异常特征的级联是如何发生的 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获得的血细胞 在治疗前后诊断出 RA 患者，以确定有效的 RA 治疗是否会缓解 这些异常特征。总而言之，该项目将描绘一系列分子事件，导致 RA 临床症状的发展将使我们更接近 RA 的最初触发因素。