Contact PI/Project LeaderBERIN, MARIA CECILIA Other PIs
Awardee OrganizationNORTHWESTERN UNIVERSITY AT CHICAGO
Description
Abstract Text
Food protein induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a usual onset in
infancy. FPIES is recognized as an allergic emergency due to severe vomiting, and shock-like symptoms within
1-4 hours of ingestion of the causative food. Symptoms of FPIES resolve within hours following acute exposure
and days following chronic exposure; endoscopy and biopsy of gastrointestinal mucosa are not routinely
performed for the confirmation of diagnosis that is based on the recognition of the constellation of symptoms.
Diagnosis in infancy is based on clinical history, and oral food challenges (OFC) are performed to determine if
outgrowth has occurred. OFC are performed in hospital, with intravenous access in place for rapid fluid
resuscitation. In addition to being highly resource-intensive, they are limited in availability and extremely
unpleasant for the patient and the caregivers, due to the severity of the gastrointestinal symptoms. There is an
unmet need for better approaches for diagnosis, as well as an understanding of the underlying pathophysiology.
In Aim 1, we will randomize participants 1:2 to standard OFC or a novel low-dose multi-day challenge protocol,
in which individuals with a history of FPIES will be challenged on Day 1 with a low-dose (300 mg protein) OFC,
which we expect to be tolerated by most individuals with active FPIES. They will then continue with a daily 300
mg challenge at home for a total of 7 days, while monitoring symptoms. On day 8, participants will return for a
re-evaluation and biospecimen collection. If no objective symptoms were recorded during the at-home challenge,
a regular 3 g OFC will be performed. Objective symptoms at any point of the protocol will result in stopping of
the challenge. We anticipate that the majority of those who will react to the OFC will develop relatively mild but
objective gastrointestinal symptoms (vomiting, diarrhea) during the at home dosing. In Aim 2, we will perform
high dimensional T cell profiling of T cells activated by the low dose chronic antigen challenge. FPIES is
associated with a lack of circulating detectable food-specific T cells, however during symptomatic reactions there
is a systemic innate immune cell activation as well as a Th17 cytokine signature detectable in the plasma,
suggesting a role for tissue resident T cells. As is observed with gluten challenge in celiac disease, we expect to
see an expansion of gut-resident T cells in the periphery in response to a multi-day food challenge. We will sort
these cells and perform spectral cytometry, bulk RNAseq, and single cell RNAseq to generate a full
understanding of the role of these cells in FPIES reactions. In Aim 3, we will examine the role of the purine
metabolism pathway as the mechanistic link between T cell activation and vomiting symptoms in FPIES.
Serotonin from enterochromaffin cells (EC) is thought to drive activation of vagal afferents leading to vomiting,
and EC are responsive to purine metabolites that are elevated during FPIES reactions. In Aim 3, we will use
gastrointestinal biopsies to study the immune regulation of serotonin release from ECs via the purine pathway.
Successful completion of our aims will directly improve patient care and advance our understanding of FPIES.
Public Health Relevance Statement
FPIES is a non-IgE-mediated food allergy with unknown pathophysiology, and the only diagnostic test is an oral
food challenge performed in a hospital setting which can result in severe symptoms. In this project, we propose
a new low-dose multi-day food challenge protocol that we anticipate will generate milder symptoms, and will
release mucosal T cells into the periphery for high dimensional single-cell analysis. This clinical and mechanistic
study will improve care for patients with FPIES by improving diagnostics and revealing novel immune pathways
of disease.
National Institute of Allergy and Infectious Diseases
CFDA Code
855
DUNS Number
005436803
UEI
KG76WYENL5K1
Project Start Date
23-August-2022
Project End Date
31-May-2027
Budget Start Date
01-June-2024
Budget End Date
31-May-2025
Project Funding Information for 2024
Total Funding
$353,605
Direct Costs
$300,933
Indirect Costs
$52,672
Year
Funding IC
FY Total Cost by IC
2024
National Institute of Allergy and Infectious Diseases
$353,605
Year
Funding IC
FY Total Cost by IC
Sub Projects
No Sub Projects information available for 5U01AI170836-03
Publications
Publications are associated with projects, but cannot be identified with any particular year of the project or fiscal year of funding. This is due to the continuous and cumulative nature of knowledge generation across the life of a project and the sometimes long and variable publishing timeline. Similarly, for multi-component projects, publications are associated with the parent core project and not with individual sub-projects.
No Publications available for 5U01AI170836-03
Patents
No Patents information available for 5U01AI170836-03
Outcomes
The Project Outcomes shown here are displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed are those of the PI and do not necessarily reflect the views of the National Institutes of Health. NIH has not endorsed the content below.
No Outcomes available for 5U01AI170836-03
Clinical Studies
No Clinical Studies information available for 5U01AI170836-03
News and More
Related News Releases
No news release information available for 5U01AI170836-03
History
No Historical information available for 5U01AI170836-03
Similar Projects
No Similar Projects information available for 5U01AI170836-03