Build to LEAD – Building partnerships to Link the Exposome to Autoimmune Disease

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.

Grant Number: 1R21AR084042-01
NIH Institute/Center: NIH
Principal Investigator: Jane Buckner