Build to LEAD – Building partnerships to Link the Exposome to Autoimmune Disease

项目总结/摘要 环境健康研究人员已经确定了在发展中的重要作用， 许多复杂疾病的进展，包括自身免疫。我们和其他人已经确定了 在特定的暴露之间，如野火烟雾和EB病毒，以及免疫系统的变化 在有和没有自身免疫性疾病的人身上。拟议研究的总体目标是建立一个 一个跨学科的合作研究小组，专注于了解在自身免疫性疾病中的作用， 疾病，特别是类风湿性关节炎（RA）和系统性红斑狼疮（SLE），参与 Exposome in Autoimmune Diseases Collaborating Teams，EXACT Network。在具体目标1中，我们将制定一个 位于西雅图的贝纳罗亚研究所（BRI）和俄克拉荷马州之间建立了牢固的正式伙伴关系 医学研究基金会（OMRF）在俄克拉荷马州市，以定义之间的关联，广泛的 RA和SLE的环境暴露和临床严重程度/发作。BRI和OMRF保持着一些最大的 来自RA和SLE个体的样本的国家生物储存库，具有疾病的纵向测量， 重新联系参与者。我们将协调与这些自身免疫性疾病的临床特征相关的数据 跨站点（例如，自身抗体和严重程度测量），并在每个研究中心实施新的共享方案， 收集与麻烦的测量相关的数据和样本。在目标2中，我们将组织和主办 为自身免疫性疾病研究人员、环境卫生和毒理学专家举行了两次首脑会议， 遗传学家、临床医生、患者、EXACT网络站点和其他利益相关者。第一次首脑会议将确定和 优先考虑对这一新兴领域至关重要的问题，第二次峰会将设计一个 执行计划以解决这些问题。在目标3中，我们将开发所需的团队和资源， 进行两项初步研究，以调查RA和SLE中的作用。第一项试点研究提出， 以确定野火烟雾对RA免疫状况的影响，第二个试点将确定 使用地理编码的SLE环境影响。这项工作将建立协作团队和研究 框架准备好解决EXACT网络的未来优先事项，重点是了解 暴露在塑造自身免疫性疾病的发展和进展中起作用。

Project Summary/Abstract Environmental health researchers have identified a substantial role of the exposome in development and progression of many complex diseases, including autoimmunity. We and others have identified relationships between specific exposures, such as wildfire smoke and Epstein-Barr virus, and changes to the immune system in people with and without autoimmune disease. The overarching goal of the proposed studies is to establish a collaborative interdisciplinary research team focused on understanding the role of the exposome in autoimmune disease, specifically rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), to participate in the Exposome in Autoimmune Diseases Collaborating Teams, EXACT Network. In Specific Aim 1, we will develop a strong, formalized partnership between the Benaroya Research Institute (BRI) in Seattle and the Oklahoma Medical Research Foundation (OMRF) in Oklahoma City to define associations between a broad spectrum of environmental exposures and clinical severity/flares in RA and SLE. BRI and OMRF maintain some of the largest national biorepositories of samples from individuals with RA and SLE, with longitudinal measures of disease and ability to recontact participants. We will harmonize data related to clinical features of these autoimmune diseases across sites (e.g., autoantibodies and severity measures), and implement new, shared protocols at each site for collection of both data and samples relevant to exposome measurements. In Aim 2, we will organize and host two summit meetings for autoimmune disease researchers, environmental health and toxicology experts, geneticists, clinicians, patients, EXACT Network sites, and other stakeholders. The first summit will define and prioritize questions that are of critical importance to this emerging field, and the second summit will design an implementation plan to address these questions. In Aim 3, we will develop the teams and resources needed to conduct two pilot studies to investigate the role of the exposome in RA and SLE. The first pilot study proposes to determine the impact of wildfire smoke on the immune landscape in RA and the second pilot will determine environmental influences in SLE using geocoding. This work will establish collaborative teams and a research framework ready to address the future priorities of the EXACT Network focusing on understanding the role that exposures play in shaping autoimmune disease development and progression.