Development of Foundational Collaborations and Capabilities to Advance Exposome Research in Childhood-onset Rheumatic Diseases and other Pediatric Autoimmune Conditions

项目总结 该项目的主要愿景是建立调查员和网络合作， 暴露组在儿童期风湿性疾病和其他自身免疫中作用的研究进展 条件，首要目标是创造新的研究资源和组建新的儿科团队 来自现有网络的研究人员可能对新生的“自身免疫性疾病的外切体”做出贡献 协作团队“(确切的)网络。最近的美国国家科学院、工程院和 医学报告《加强美国国立卫生研究院对自身免疫性疾病的研究》(2022)，确定了 当代自身免疫性疾病的研究努力值得特别关注的精确计划 讲话，明确支持一种包括以儿童和青少年为重点的生命过程方法。我们 寻求通过两个现有儿科网络之间的合作来解决这一重点，该网络具有广泛的 表型和生物库资源：研究者赞助的儿童关节炎和风湿病研究 联盟(CARA)，它赞助CARA注册，以及NIH/NCATS资助的基因组信息 公地(GIC)。Carra注册中心已从70个网站注册了13,000名受试者，其中近1,900人 生物库样本，是儿童风湿病最大的纵向慢性疾病登记 北美的疾病，临床数据收集和生物库在4个疾病类别：青少年 特发性关节炎，系统性红斑狼疮/混合性结缔组织病/干燥综合征， 幼年性皮肌炎，以及局限性和系统性硬皮病。GIC网络是一个合作的网络， 美国8个儿科学术医学中心参与的表型-基因型生物库工作， 具有不同条件的受试者的广泛代表性(1370万受试者，约3万基因组- 链接的表型数据，收集了160,000个生物样本)，并提供跨站点搜索以识别队列 患有和不患有风湿性或自身免疫性疾病的个体，基础设施也支持研究对象 为将来的研究招募和建立生物库。我们这个项目的目标有两个：(1)建立一个 CARA和GIC网络调查人员之间的合作框架，以增强海流 利用暴露组数据和生物库标本开展研究活动；以及(2)试行公众可获得的 将包括空气和水质量数据库在内的一些数据集暴露给中非数据中心登记处的现有数据集 而GIC则坚持。我们将制定和调整政策、协议、知情同意书、病例报告表和 专门针对纳入儿童发病风湿病暴露数据的患者调查 疾病和其他自身免疫性疾病。我们的多学科项目团队包括 儿科风湿病及暴露者、技术专家和患者代表。已完成的 该项目的目标将使新的基于团队的协作能够实施未来高质量的最佳实践 暴露了许多儿科自身免疫性疾病的研究，作为未来确切网络的一部分。

PROJECT SUMMARY The primary vision of this project is the establishment of investigator and network collaborations that will advance study of the role of the exposome in childhood-onset rheumatic diseases and other autoimmune conditions, with an overarching goal of creating new research resources and forming new teams of pediatric investigators from existing networks that can contribute to the nascent “EXposome in Autoimmune Disease Collaborating Teams” (EXACT) network. The recent National Academies of Science, Engineering and Medicine report “Enhancing NIH Research on Autoimmune Disease” (2022), which identified “gap areas” in contemporary research efforts of autoimmune diseases that the EXACT-PLAN Notice of Special Interest addresses, specifically endorses a life-course approach that includes a focus on children and adolescents. We seek to address this focus via collaboration between two existing pediatric networks with extensive existing phenotype and biobank resources: the investigator-sponsored Childhood Arthritis and Rheumatology Research Alliance (CARRA), which sponsors the CARRA Registry, and the NIH/NCATS funded Genomic Information Commons (GIC). The CARRA Registry has enrolled >13,000 subjects from >70 sites, with nearly 1,900 biobanked specimens, and is the largest longitudinal chronic disease registry for childhood-onset rheumatic diseases in North America, with clinical data collection and biobanking in 4 disease categories: Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus/Mixed Connective Tissue Disease/Sjogren’s Syndrome, Juvenile Dermatomyositis, and Localized and Systemic Scleroderma. The GIC network is a cooperative, phenotype-genotype biobanking effort with 8 participating pediatric academic medical centers across the US, with broad representation of subjects with differing conditions (13.7 million subjects, ~30,000 with genome- linked phenotypic data, 160,000 biospecimens collected) and provides search across sites to identify cohorts of individuals with and without rheumatic or autoimmune diseases, with infrastructure also supporting subject recruitment and biobanking for future studies. Our aims for this project are two-fold: (1) Establish a collaborative framework between investigators of the CARRA and GIC networks for augmenting current research activities with exposome data and biobank specimens; and (2) pilot the linkage of publicly available exposome data sets, including air and water quality databases, to existing data sets that the CARRA Registry and GIC maintain. We will develop and adapt policies, protocols, informed consents, case report forms, and patient surveys that are specifically targeted to incorporating exposome data for childhood-onset rheumatic diseases and other autoimmune conditions. Our multi-disciplinary project team includes researchers in pediatric rheumatology and the exposome, technology experts, and patient representatives. Completion of the aims of this project will enable new team-based collaborations to conduct future high-quality, best-practices exposome research for many pediatric autoimmune diseases as part of the future EXACT network.