# Effects of IgE Blockade on T Cells in Food Allergy

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $392,500

## Abstract

Project Summary: Effects of IgE Blockade on T Cells in Food Allergy
 Food allergies can lead to near-fatal or fatal anaphylaxis. Approximately 30% of food allergic individuals have
multiple food allergies. Although many studies have evaluated the efficacy of oral immunotherapy (OIT) for
single foods, studies evaluating OIT to multiple foods (multi-OIT) have been limited due to efficacy and safety
concerns. Multifood allergic individuals could benefit from treatment, and omalizumab (anti-IgE blockade
therapy) potentially mitigates their risk for IgE-mediated allergic reactions. A few groups, including ours, have
demonstrated important immunophenotypic and functional biomarker changes induced by single-allergen OIT
in T cell subsets. The salient findings from these reports show: increases in the numbers and function of
regulatory T cells (Treg); reprogramming of T helper 2 cells (Th2) to the T helper 1 (Th1) subtype; and anergy in
allergen-specific Th2 cells. It is of great interest to identify T cell immune biomarker changes while multi-OIT is
given to multi-allergic individuals to track desensitization, a lack of clinical reactivity with regular antigen (Ag)
exposure, as distinct from sustained unresponsiveness, in which the patient exhibits a long-term and perhaps
permanent loss of reactivity to Ag that is independent of continued Ag exposure. Therefore, we have
performed a randomized, controlled, phase 2 study in a cohort of multifood allergic participants (Multi
Immunotherapy to Test Tolerance and Xolair, ClinicalTrials.gov Identifier: NCT02626611, n=70 participants):
peripheral blood mononuclear cells and plasma samples were collected and stored throughout the duration of
study. We propose to use these samples and two sets of matched controls for this project.
 Our main hypothesis is that multi-OIT results in marked downmodulation of Th2 function and concomitant
enhancement in Th1 and Treg function, and that these changes will be associated with sustained
unresponsiveness and, to a lesser extent, desensitization. To test this hypothesis, we propose to: (Aim 1)
Characterize the immunophenotypic and functional changes induced by multi-OIT in total and allergen-specific
T cell populations in multi-allergic study participants; (Aim 2) Use MHC class II multimer-based methods to sort
allergen-specific single cells, and perform targeted RNA-Seq to investigate their molecular signatures and
clonal ancestry at single-cell resolution; and (Aim 3) Quantify epigenetic changes (i.e., methylation of CpG
islands) in key genes (i.e., FOXP3, IL4, IFNg, IL10) to assess possible links between the methylation and the
desensitization and sustained unresponsiveness resulting from OIT.
 The results from this study of T cell phenotype, function and epigenetics will enable us: to identify which of
these immune features will be most useful as signatures of multi-OIT-induced desensitization and sustained
unresponsiveness; to identify patterns of changes in T cells that...

## Key facts

- **NIH application ID:** 10199745
- **Project number:** 5R01AI140134-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Kari C. Nadeau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2018-07-16 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199745

## Citation

> US National Institutes of Health, RePORTER application 10199745, Effects of IgE Blockade on T Cells in Food Allergy (5R01AI140134-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10199745. Licensed CC0.

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