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 has been 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. We address this focus via collaboration between the EXACT-PLAN consortium (initiated August 2023) and our two existing pediatric networks, which have pre-existing, extensive 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). Over the first two years of EXACT-PLAN, we have established collaborations that take the initial steps to advance our understanding of the role of exposures in the development and course of autoimmune diseases (AIDs), resulting in a shared definition of `Pillars of Exposome Studies in Autoimmunity' to help drive further EXACT collaborations. At the same time, we have made substantial progress towards fulfilling our aims for the parent project, which 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 are further developing and adapting policies, protocols, informed consents, case report forms, and patient surveys that are specifically targeted to incorporate exposome data for childhood-onset rheumatic diseases and other autoimmune conditions. For this supplement, we will further enhance collaborations between our two pediatric networks (CARRA and GIC) with other EXACT-PLAN projects, focusing on the development of geographically diverse pediatric cohorts for exposome-wide association studies, including for both disease-affected and as yet unaffected children and adolescents. To facilitate collaborations with our EXACT-PLAN colleague projects, we follow a near-term, shared vision of creating capabilities to conduct large-scale, exposure-wide association studies and a longer-term focus on achieving the four pillars of exposome studies in autoimmunity that were defined in the initial phase of EXACT-PLAN. For this supplement, as we further collaborate within NIH's planned “EXposome in Autoimmune Disease Collaborating Teams” (EXACT) network, we simultaneously pilot enhanced, longitudinal geographic histories and exposome-ready cohort definition capabilities for the GIC research population at Boston Children's Hospital (BCH). 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 (14 million subjects, ~24,000 with genome-linked phenotypic data, 180,000 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. At BCH, GIC enrolls 2.9 million subjects of which ~7,000 have genome-linked phenotypic data, with ~60,000 biospecimens collected. To enable longitudinal geospatial analyses, we will use the supplement period to explore local administrative linkages for geocoding as well as pilot BCH subject surveys, in a manner that will be readily extensible to other GIC sites outside of BCH. During this project period, we also plan to further engage with other EXACT-PLAN awardees in various capacities, specifically: (1) Continue to collaborate closely on EXACT-PLAN geospatial analyses (John Pearce, PI, Medical University of South Carolina) and establish new collaborations led by this group with the NIH- funded “Network for Exposomics in the United States” (NEXUS; U24ES036819); (2) Identify unaffected pediatric cohorts at the BCH GIC for collaborations with EXACT-PLAN colleagues studying the effect of exposures in pre-clinical rheumatic disease populations (systemic lupus erythematosus, rheumatoid arthritis; Jill Norris, PI, Colorado School of Public Health); (3) Identify and assist with recruitment of BCH GIC and CARRA subjects with Juvenile Idiopathic Arthritis for a remote `ImmuneTracker' mobile app pilot (Wilson Liao, PI, University of California, San Francisco); and (4) Identify pediatric AID cohorts at BCH GIC pertaining to T1DM and celiac disease (Brigitte Norris, PI, University of Colorado). 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 further 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.