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

项目摘要 该项目的主要愿景是建立调查员和网络合作， 儿童期风湿性疾病和其他自身免疫性疾病中的免疫调节基因组作用的研究进展 条件，总体目标是创造新的研究资源，形成新的儿科团队 来自现有网络的研究人员可以为新生的“自身免疫性疾病中的暴露体”做出贡献， 协作团队”（EXACT）网络。最近，美国国家科学院、工程院和 医学报告“加强NIH对自身免疫性疾病的研究”（2022年），该报告确定了 自身免疫性疾病的当代研究工作， 特别赞同一种包括以儿童和青少年为重点的终生办法。我们 寻求通过两个现有儿科网络之间的合作解决这一重点， 表型和生物样本库资源：美国儿童关节炎和流变学研究 赞助CARRA注册的CARRA联盟和NIH/NCATS资助的基因组信息 Commons（GIC）. CARRA登记研究已从>70个研究中心招募了> 13，000名受试者，其中近1，900名 生物库标本，是最大的纵向慢性疾病登记的儿童发病风湿性关节炎 在北美的疾病，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， 青少年皮肌炎，局限性和系统性硬皮病。GIC网络是一个合作的， 表型-基因型生物库工作与美国8个参与儿科学术医学中心， 具有广泛代表性的不同条件的受试者（1370万受试者，约30，000人具有基因组， 关联的表型数据，收集了160，000份生物标本），并提供跨研究中心的检索以识别队列 有和没有风湿性或自身免疫性疾病的个人，基础设施也支持主题 招募和生物样本库以供未来研究使用。我们在这个项目上的目标有两个：（1）建立一个 CARRA和GIC网络研究人员之间的合作框架， 研究活动与麻烦的数据和生物库标本;和（2）试点的链接， 包括空气和水质量数据库在内的复杂数据集与CARRA登记处 和GIC保持。我们将制定和调整政策、方案、知情同意书、病例报告表， 专门针对合并儿童期发作的风湿性关节炎的麻烦数据的患者调查 疾病和其他自身免疫性疾病。我们的多学科项目团队包括研究人员， 儿科风湿病学和儿科专家、技术专家和患者代表。完成 该项目的目标是使新的基于团队的合作能够在未来进行高质量的最佳实践 作为未来EXACT网络的一部分，许多儿科自身免疫性疾病的棘手研究。

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.