The Exposome in Rheumatoid Arthritis and Systemic Lupus Erythematosus: EXACT Network Planning

项目总结 这是一项探索性发展拨款，旨在设计、开发和实施未来 国家、跨学科、协作、团队科学研究网络，将推动对 自身免疫性疾病中的暴露体(自身免疫性疾病中的暴露体合作小组，Exposome)。我们 建议计划对类风湿性关节炎(RA)临床前阶段的暴露组进行研究 系统性红斑狼疮(SLE)。我们断言，在曝光之前测量曝光体是很重要的 疾病的发展，以确保我们正在测量的东西在疾病之前，而不是结果 (如果对患病个体进行测量，则可能会发生这种情况)。这将使我们能够 推断暴露于类风湿关节炎和系统性红斑狼疮风险的暂时性和潜在因果关系。这 可以使用预期的高危个体队列来实现，这些高危个体被跟踪以发展 临床疾病(即可分类的类风湿性关节炎和系统性红斑狼疮)，我们有很长的工作历史。该中心的调查人员 科罗拉多大学安舒茨医学院(诺里斯、霍勒斯和亚伯拉罕)将与调查人员在 俄克拉荷马医学研究基金会(詹姆斯和门罗)对相关的景观进行分析 现有1)资源、人口、数据库、登记册、储存库和联合体，2)有关数据 曝光，3)曝光组实验室，4)曝光组分析技术。这将提供一个背景 我们将用它来计划一个新项目的活动，以研究RA和SLE的曝光组。作为该计划的一部分 规划过程中，我们将举行一次揭露专家和调查人员与队列/人口的峰会 风湿性关节炎和系统性红斑狼疮的高危人群，发展和扩大现有的研究合作，以进行 这些疾病暴露的前瞻性研究。我们将利用我们现有的新的风险队列 被跟踪发展成可分类的类风湿关节炎和系统性红斑狼疮以探索 统一调查问卷和生物标志物数据，并进行二级数据分析，以支持 未来精确网络的假设和研究策略。我们将与科学公司等利益攸关方接触 或在类风湿性关节炎和系统性红斑狼疮领域的专业协会和患者和患者倡导者 翻译为准确的网络研究议程提供信息。这项提案的总体目标是计划研究 战略和发展合作伙伴关系、基础设施和能力，以实现 未来协作确切的网络，并制定支持研究框架和策略 研究、协作研究项目和站点之间的协调。具体目标1.开展一项 多管齐下，以确定需求和目前可用的资源，以前瞻性和 有效测量类风湿性关节炎和系统性红斑狼疮的曝光体(通过景观分析)。具体目标2.设计一种 一项跨学科的前瞻性研究，探讨暴露组在类风湿关节炎和系统性红斑狼疮病因中的作用 研究团队、严格的曝光测量和新颖的分析方法。

PROJECT SUMMARY This is an exploratory developmental grant aimed at the design, development, and implementation of a future national, interdisciplinary, collaborative, team science research network that will advance the study of the exposome in autoimmune diseases (Exposome in Autoimmune Diseases Collaborating Teams, EXACT). We propose to plan a study of the exposome during the pre-clinical period of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We assert that it is important to measure the exposome prior to the development of disease to ensure that what we are measuring precedes the disease and is not a consequence of the disease (which might happen if the exposome were measured in diseased individuals). This will allow us to draw inference about the temporality and potential causality of exposures on the risk of RA and SLE. This can be accomplished using prospective cohorts of at-risk individuals that are followed for the development of clinical disease (ie classifiable RA and SLE) with which we have a long history of working. Investigators at the University of Colorado Anschutz Medical Campus (Norris, Holers and Abraham) will work with investigators at the Oklahoma Medical Research Foundation (James and Munroe) to conduct a landscape analysis of relevant existing 1) resources, populations, databases, registries, repositories and consortia, 2) data on relevant exposures, 3) exposome laboratories, and 4) exposome analytic techniques. This will provide a background that we will use to plan activities for a new project to study the exposome in RA and SLE. As part of the planning process, we will hold a summit of exposome experts and investigators with cohorts/populations of individuals at-risk for RA and SLE, to develop and expand existing research collaborations to conduct a prospective study in the exposome of these diseases. We will use our existing novel cohorts of at-risk individuals who have been followed to the development of classifiable RA and SLE to explore feasibility of harmonization of questionnaire and biomarker data and conduct secondary data analysis to support the hypothesis and research strategy of the future EXACT Network. We will engage stakeholders such as scientific or professional associations and patients and patient-advocates in the areas of RA and SLE for better translation to inform the EXACT Network research agenda. The overall goal of this proposal is to plan research strategies and develop partnerships, infrastructure, and capabilities needed to address the major goals of a future collaborative EXACT network and to develop a research framework and strategies to support coordination among studies, collaborative research projects, and sites. Specific Aim 1. To conduct a multipronged approach to determine the needs and currently available resources to prospectively and effectively measure the exposome in RA and SLE (via a landscape analysis). Specific Aim 2. To design a prospective study to examine the role of the exposome in the etiology of RA and SLE, with an interdisciplinary research team, rigorous exposome measurements and novel analytic approaches.