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

Boston Children'S Hospital, Boston MA

Investigators

Abstract

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.