# IgE antibodies to the mammalian oligosaccharide galactose-alpha-1, 3-galactose (alpha-gal): immunology, epidemiology and relevance to allergic and inflammatory disease

> **NIH NIH R37** · UNIVERSITY OF VIRGINIA · 2021 · $622,802

## Abstract

SUMMARY
The syndrome of delayed anaphylaxis to red meat, i.e. the alpha-gal syndrome (AS), is found exclusively in
patients who have serum IgE antibody (ab) to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal).
This form of sensitization is related to bites of the tick Amblyomma americanum, however other ticks appear to
be relevant in other countries. The objective of the studies proposed here is to investigate the epidemiology,
etiology, immunology and clinical features of AS which is now known to be common in a large area of the USA.
The studies focus on three aspects of the syndrome. Firstly we will use a detailed map of the cases of AS to
compare with maps of tick-related diseases and the distribution of ticks. The serologic response to alpha-gal
will be compared from AS cases in participating sites from different parts of the country. Additionally, to
investigate the possibility that the Rickettsiae group of obligate intracellular bacteria, such as Rickettsia
amblyommii or Ehrlichia chaffeensis, could be relevant to AS sensitization we will carry out assays for specific
IgG ab. Secondly, in the area where there is a high prevalence of IgE to alpha-gal there are many individuals
who are sensitized but either do not report symptoms or report delayed symptoms that are not recognized as
allergic. These include patients with repeated episodes of abdominal pain. Our primary hypothesis about the 3-
5 hour delay in the onset of symptoms is that this reflects the time taken to process dietary mammalian
glycoprotein and/or glycolipids lipids to a size that readily penetrates into tissue, for example the size of LDL
(~20 nm). Another disease not traditionally considered to be related to allergy is coronary artery disease. In a
preliminary investigation we have found that the presence of detectable levels of IgE to alpha-gal is
significantly associated with the burden of atherosclerosis in a cohort of subjects in central Virginia. This study,
which utilized intravascular ultrasound (IVUS), also demonstrated an association with coronary plaques which
had unstable, i.e. high risk, features. We will further investigate this association in a larger cohort at our
institution and extend the investigation to subjects in other regions with high prevalence of alpha-gal
sensitization. The primary objective of the third aim is to obtain better information about the B cells that relate
to the antibody response to alpha-gal. Preliminary data using mass cytometry suggests that subjects with AS
have a population of plasmablasts that can respond to alpha-gal. The proposed studies will further investigate
these cells with an expanded mass cytometry bead panel and use multiple samples in a single batch. In
conjunction with parallel studies employing antibody deep sequencing, collective results are expected to shed
insight into the B cell populations that produce `natural' antibodies to alpha-gal, i.e. IgM and IgG2 antibody, as
well as those B cells that produ...

## Key facts

- **NIH application ID:** 10190780
- **Project number:** 5R37AI020565-37
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** THOMAS A. PLATTS-MILLS
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $622,802
- **Award type:** 5
- **Project period:** 1984-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190780

## Citation

> US National Institutes of Health, RePORTER application 10190780, IgE antibodies to the mammalian oligosaccharide galactose-alpha-1, 3-galactose (alpha-gal): immunology, epidemiology and relevance to allergic and inflammatory disease (5R37AI020565-37). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10190780. Licensed CC0.

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