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.

Project Narrative While genetics are partially predictive of who will develop autoimmune disease, it is well understood that other factors in our lived environment play a role in disease development and severity. Our EXACT-PLAN proposal aims to design studies of people with systemic lupus erythematosus and rheumatoid arthritis to understand the way that environmental exposures like smoking, exposure to wildfire smoke, social determinants of health, occupational exposures, UV, pesticides and others can influence the severity of disease and frequency of flares.