Build to LEAD - Building partnerships to Link the Exposome to Autoimmune Disease (Administrative Supplement)

SUMMARY
This is a request for an Administrative Supplement for 1R21AR084042 “Build to LEAD – Building partnerships
to Link the Exposome to Autoimmune Disease. The proposed studies for the Administrative Supplement are
within the scope of the active parent grant, which is focused on establishing collaborative teams within the
Exposome in Autoimmune Diseases Collaborating Teams (EXACT) Network to study how environmental
exposures influence autoimmune disease susceptibility, onset and outcomes, and to perform pilot analyses
relating specific environmental exposures to immune outcomes. The objectives of the Administrative Supplement
are: 1) Expand a parent grant pilot study of the impact of wildfire smoke on the immune system to multiple
autoimmune diseases and deepen our understanding in healthy participants; 2) Extend the parent grant
geocoding pilot studies to investigate the role of per- and polyfluoroalkyl substances (PFAS) exposure on
immune outcomes using banked samples and existing geospatial data from established healthy and autoimmune
cohorts; and 3) Continue to provide leadership of the EXACT-PLAN Network, focusing on building new
collaborations within the network as well as with external exposome experts, with the overarching goal to
determine priorities for future EXACT Network efforts. In Specific Aim 1, cytometric analyses will be performed
on existing banked peripheral blood mononuclear cells to determine whether response to wildfire smoke differs
by immunotype or age in healthy individuals. The immune response to wildfire smoke will also be examined in
people with autoimmune disease. In Specific Aim 2, PFAS will be measured in existing banked serum samples
to determine whether PFAS levels in peripheral blood are associated with immunotypes in healthy individuals.
Geospatial data will be used to determine whether PFAS levels in drinking water are associated with autoimmune
disease prevalence. In Specific Aim 3, a half-day symposium focused on the exposome and autoimmune disease
will be organized for the annual Federations for Clinical Immunology Societies (FOCIS) meeting in June 2026.
EXACT-PLAN investigators and colleagues in related groups (e.g., NEXUS, All of Us) will present work
highlighting the exposome in autoimmune disease at this public-facing meeting, where all FOCIS attendees are
welcome. Collectively this work will advance our understanding of the role of the exposome in the development
and progression of autoimmune disease and help the EXACT-PLAN Network determine priorities for future
exposome studies in the setting of autoimmune disease.

Grant Number: 3R21AR084042-01S2
NIH Institute/Center: NIH
Principal Investigator: Jane Buckner