# Immunologic basis of phenotypic heterogeneity in peanut allergy

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $391,986

## Abstract

Project 2-Summary
There is heterogeneity in many aspects of peanut allergy (PA), including the dose of peanut that triggers
symptoms (the threshold), the severity of symptoms that are induced, and the type of symptoms (target
organ(s)) that are triggered. A significant minority (up to 20%) will outgrow their PA, while the majority retains
clinical reactivity. We propose that this natural heterogeneity in the clinical phenotype of PA is a valuable
opportunity to understand immune mechanisms contributing to disease. We hypothesize that distinct immune
responses at the level of IgE, IgG4, CD4+ T cells, and basophils underlie important clinical heterogeneity, and
furthermore we hypothesize that these distinct immune profiles form a basis for prognosis of PA. Through the
Clinical Core, we will have access to 200-250 subjects undergoing oral food challenge for PA who have a low
or high threshold of reactivity to peanut, or who are not allergic. We will also have access to 98 high-threshold
subjects randomized to receive sub-threshold peanut in the diet (or continue avoidance), and who will have a
diverse set of clinical outcomes over the 2.5 years that they are studied. We will perform high dimensional
immune profiling on these subjects to identify pathways linking immune and clinical responses to peanut. We
have found that bioinformatics analysis of IgE binding to epitopes in milk allergens can predict not only clinical
phenotype of milk allergy, but accurately predict treatment success after milk oral immunotherapy. We will
apply this approach to test if epitope binding can predict clinical reactivity to peanut, and predict response to
dietary intervention. We have also identified that the magnitude and differentiation of the peanut-specific Th2
response is highly heterogeneous in PA subjects. We will determine the clinical implications of Th2
heterogeneity within this diverse cohort, using a combination of CD154-based detection and phenotypic
analysis of peanut-responsive T cells by flow cytometry, and multiplex cytokine assays. We have developed
CyTOF-based approaches to study the response of cells in whole blood to peanut, and have published as well
as preliminary data demonstrating that we can identify signaling and activation in basophils and other cell types
not only in vitro but also in vivo. We hypothesize that broad profiling of the activation of cells in whole blood by
CyTOF will identify novel communities of responding cells that discriminate between key clinical phenotypes of
PA. The successful completion of our project will build a clinical-immune network of PA that overlays a detailed
clinical phenotype over a high dimensional network of peanut-specific antibodies, T cells, and effector cell
responses. We anticipate that this clinical-immune network will not only reveal mechanisms, but will be an
essential tool for guiding personalized management and treatment strategies for PA.

## Key facts

- **NIH application ID:** 9934155
- **Project number:** 5U19AI136053-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Cecilia Berin
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,986
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934155

## Citation

> US National Institutes of Health, RePORTER application 9934155, Immunologic basis of phenotypic heterogeneity in peanut allergy (5U19AI136053-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934155. Licensed CC0.

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