# Suppression of basophil activation by IgE glycovariants

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $109,609

## Abstract

Project Summary
Most allergic reactions are caused by immunoglobulin E (IgE) antibodies that are specific for allergens and
trigger potent inflammatory responses mediated by mast cells and basophils. IgE binds to the high affinity
receptor (FcεRI) expressed on these allergic effector cells, making this a key interaction that is common to
many different allergen-specific responses. The anti-IgE therapeutic antibody (Omalizumab) is currently used
to treat allergic asthma and chronic idiopathic urticaria in patients. We determined the structure of the
Omalizumab Fab bound to the IgE-Fc, clarifying how Omalizumab blocks IgE interactions with both receptors.
We also designed an IgE-Fc glycosylation mutant that does not bind Omalizumab, but retains interactions with
high and low affinity IgE receptors. This IgE glycovariant can be co-administered with Omalizumab, to replace
the cell-bound IgE, exchanging allergen-reactive IgE with a non-reactive variant. This co-treatment of cells
provides synergistic inhibition that is more potent at blocking basophil activation than either inhibitor alone. Our
IgE glycovariant, which incorporates a single additional N-linked glycosylation site into the IgE-Fc, also shows
more potent inhibition of basophils on its own as compared to the wild type IgE-Fc. The inhibition does not
require direct competition for FceRI binding by “allergic” IgE. We hypothesize that carbohydrate-specific
inhibitory receptors, such as members of the Siglec family, may be engaged by the IgE glycovariant to block
FcεRI signaling. In this proposal, we will explore the impact of IgE glycosylation on the inhibition of human
basophil activation, both with and without concomitant Omalizumab treatment, and identify the mechanisms by
which IgE glycovariants suppress FceRI-dependent activation of allergic inflammatory cells.

## Key facts

- **NIH application ID:** 10091046
- **Project number:** 3R01HL141493-03S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Theodore S Jardetzky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $109,609
- **Award type:** 3
- **Project period:** 2018-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10091046

## Citation

> US National Institutes of Health, RePORTER application 10091046, Suppression of basophil activation by IgE glycovariants (3R01HL141493-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10091046. Licensed CC0.

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