# Regulation of IgE and Atopic Itch

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $645,308

## Abstract

PROJECT SUMMARY
The current paradigm of allergic inflammation asserts that allergen crosslinking of FcεR1-bound to allergen-
specific IgE leads to mast cell and basophil degranulation and release of effector molecules like histamine and
leukotrienes. AD is a classic allergic disorder like asthma and food allergy and the most common chronic illness
of childhood and is often a lifelong disease1. However, the specific role of IgE in AD pathogenesis is not well
characterized and controversial2,3. In 2021, the Kim lab showed that IgE-mediated mast cell stimulation triggers
histamine-induced itch in the steady state. Intriguingly, under AD-like conditions, IgE triggers basophils to elicit
non-histaminergic itch through the mediator leukotriene C4 (LTC4). Patients with AD demonstrated increased
IgE reactivity and basophil activation in association with acute itch flares4. In parallel, our studies demonstrated
for the first time that IgE glycosylation, and specifically sialic acid, is a determinant of IgE pathogenicity.
Increased sialic acid content of IgE resulted in more significantly mast cell degranulation in both murine and
human models5. Our studies raised the possibility that pathogenicity of IgE can be variably regulated to control
cellular responses through alterations in glycosylation. Taken together with the variations in IgE cellular
interactions in steady state and AD-associated itch demonstrated by Dr. Kim's group, our central hypothesis is
that unique IgE glycosylation patterns result in enhanced mast cell-mediated itch in the steady state, while also
promoting basophil-mediated acute itch flares in AD. We will test our central hypothesis and attain the objective
of the application by pursuing the following three specific aims: 1) Do different glycoforms of IgE mediate itch in
the steady state?; 2) Does AD-associated inflammation result in the production of different glycoforms of IgE?;
3) Identify itch-specfic IgE glycosylation patterns in human AD. The role of specific IgE glycosylation in
contributing to itch in AD is unknown and regulation of these processes is poorly defined. The work from this
proposal will allow us to pursue our long-term goal of establishing how IgE glycosylation and basophils can be
targeted to yield innovative treatments for itch and AD. The overall objective of our proposal is to test the
mechanisms by which IgE glycosylation affects mast cell and basophil activation, respectively, contributing to
the development of different forms of itch. There is an urgent need to decrypt the role of IgE glycosylation in AD
in an effort to yield more effective therapies for AD-associated itch. These studies will have impact beyond AD
to diseases in which IgE and itch are implicated including allergic contact dermatitis, bullous pemphigoid, and
chronic spontaneous urticaria among others with shared mast cell and/or basophil pathologies.

## Key facts

- **NIH application ID:** 10887528
- **Project number:** 5R01AI167933-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Michelle E Conroy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,308
- **Award type:** 5
- **Project period:** 2022-09-19 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887528

## Citation

> US National Institutes of Health, RePORTER application 10887528, Regulation of IgE and Atopic Itch (5R01AI167933-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10887528. Licensed CC0.

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