NIAMS Clinical Research Center for Rheumatoid Disease

描述(由申请人提供)：南卡罗来纳医科大学将建立一个多学科临床研究中心(MCRC)，用于研究非裔美国人的风湿性疾病。MCRC将重点关注硬皮病(SSC)和系统性红斑狼疮(SLE)，这两种风湿性疾病对非裔美国人社区的影响不成比例。在风湿学、生物统计学/流行病学和卫生服务研究这三个关键领域的杰出领导地位，为在这一研究不足的患者群体中成功设计和实施有意义的临床研究提供了一个框架。提出了三个项目和三个支持核心。项目A旨在研究转化生长因子-β和鞘磷脂信号通路在SSC和正常成纤维细胞中的相互作用。拟议的研究将阐明这一迄今未知的相互作用，以阐明转化生长因子-β信号与其他细胞信号通路整合导致纤维化的机制。项目B涉及一个未得到充分研究的重要领域，即患有系统性红斑狼疮的女性青少年的心理社会问题，她们中的大多数是非洲裔美国人。MCRC调查人员将评估适应过程与适应和与健康相关的生活质量之间的联系，并将进行一项旨在提高这些患者的适应和生活质量的干预性试验。项目C将解决狼疮性肾炎发病率不同的种族趋势这一重要问题。非裔美国人狼疮患者的死亡率有所增加，而高加索人狼疮患者的死亡率保持稳定，这种差异不能仅由社会经济地位的差异来解释。利用卡罗莱纳州狼疮性肾炎研究和海岛古拉族人口的独特资源，MCRC的研究人员将研究遗传和环境对狼疮性肾炎发生和发展的影响。这些项目中的每一个，以及MCRC未来将开发的试点项目，都将由两个核心提供服务：(1)方法学核心将提供严格的方法学和生物统计学支持；(2)患者资源核心将确保MCRC调查人员接触到临床特征良好的非裔美国患者，生物样本是从他们那里获得和存储的。该MCRC将促进基础研究向临床领域的转化，支持亟需的行为研究，并对影响少数族裔和妇女的风湿病进行流行病学和卫生服务研究，从而体现NIAMS战略计划中提出的研究的“交叉”性质。

DESCRIPTION (provided by applicant): The Medical University of South Carolina will establish a Multidisciplinary Clinical Research Center (MCRC) for the Study of Rheumatic Diseases in African-Americans. This MCRC will focus on scleroderma (SSc) and systemic lupus erythematosus (SLE), two rheumatic diseases that disproportionately affect the African-American community. Outstanding leadership in three key areas - Rheumatology, Biometry/Epidemiology, and Health Services Research - provides a framework for successful design and implementation of meaningful clinical research in this understudied population of patients. Three projects and three supporting cores are proposed. Project A is designed to study the interactions between TGF-beta and sphingolipid signaling pathways in SSc and normal fibroblasts. The proposed studies will elucidate this heretofore-unknown interaction to shed light on the mechanism whereby TGF-beta signaling is integrated with other cellular signaling pathways leading to fibrosis. Project B addresses an important understudied area, namely psychosocial aspects of female adolescents with SLE, the majority of whom are African-American. MCRC investigators will assess the associations between adaptational processes and adjustment and health-related quality of life, and will conduct an interventional trial designed to enhance adjustment and quality of life for these patients. Project C will address the important issue of divergent racial trends in morbidity from lupus nephritis. Mortality has increased for African-American lupus patients while remaining stable in Caucasian lupus patients, and this divergence cannot be accounted for by differences in socioeconomic status alone. Utilizing the unique resources of the Carolina Lupus Study and the sea island Gullah population, MCRC investigators will address genetic and environmental influences on the development and progression of lupus nephritis. Each of these projects, as well as future pilot projects to be developed by the MCRC, will be served by two Cores: (1) a Methodology Core will provide rigorous methodological and biostatistical support; and (2) a Patient Resource Core will assure MCRC investigators access to a population of African-American patients who are clinically well characterized and from whom biological samples are obtained and stored. This MCRC will facilitate the translation of basic research into the clinical arena, support much needed behavioral research, and conduct epidemiology and health services research on rheumatic diseases affecting minorities and women disproportionately, thus exemplifying the "cross-cutting" nature of research proposed in NIAMS's strategic plan.