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.

项目总结