# Investigation of the prevalence, presentation and immunologic features of the α-Gal syndrome in a high-risk cohort not recruited on the basis of allergic disease

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2022 · $242,250

## Abstract

ABSTRACT
A syndrome of delayed anaphylaxis to mammalian meat, now commonly referred to as the α-Gal syndrome
(AGS), was first reported in 2009 in a cluster of cases in the southeastern United States. The reactions were
related to IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-Gal), an antigen of non-primate
mammals which is the target of IgM, IgG and IgA antibodies in healthy humans. Over the past ten years it has
become increasingly clear that tick bites, particularly bites from the lone star tick (Amblyomma americanum),
are the dominant cause of IgE sensitization to α-Gal and that AGS cases are not rare, nor limited to small
geographic areas of the United States. Based largely on cases investigated in allergy clinics, AGS is
understood to manifest with hives and/or anaphylaxis 3-6 hours after ingestion of mammalian meat, with many
patients also reporting concomitant gastrointestinal (GI) symptoms. Increasingly, however, we and other
providers in our area recognize patients who are sensitized to α-Gal that report isolated GI symptoms which
are triggered by mammalian meat and dairy. We are also seeing many α-Gal sensitized patients who carry a
diagnosis of irritable bowel syndrome (IBS), but who have responded favorably to a diet free of mammalian
meat and dairy. These observations, coupled with the fact that the population prevalence of α-Gal sIgE
sensitization is upwards of 15% in many parts of the Southeast, raise the question of whether AGS could be an
important and unrecognized cause of IBS-like presentations in our region. The goal of this proposal is to further
investigate this possibility and also to seek a better understanding of the biological factors that affect whether
an α-Gal sensitized subject will present with severe anaphylaxis, more mild IBS-spectrum GI complaints or, in
some cases, no symptoms whatsoever. Recognition of such biological factors could impact AGS management
by leading to improved tools for risk stratification and open up novel therapeutic strategies. To achieve the
study objectives we will carry out a population-based study focusing on subjects that are expected to be high-
risk for α-Gal sensitization. In contrast to most other studies of AGS, which have selectively enrolled patients
who have presented to allergy clinics, here we will recruit subjects with recent tick bites from the community
without regard to their allergic history. This approach will help address open questions about the frequency and
presentation of AGS among those who are sensitized to α-Gal. Clinical and immunologic features of these
subjects will be compared with features of AGS patients who seek care in our allergy clinic. We will also
employ a novel quantitative immunoassay to address the idea that patients who have less severe
manifestations of AGS have higher relative levels of anti-α-Gal IgG or IgA antibodies.

## Key facts

- **NIH application ID:** 10353468
- **Project number:** 1R21AI166861-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jeffrey M Wilson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,250
- **Award type:** 1
- **Project period:** 2022-07-22 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353468

## Citation

> US National Institutes of Health, RePORTER application 10353468, Investigation of the prevalence, presentation and immunologic features of the α-Gal syndrome in a high-risk cohort not recruited on the basis of allergic disease (1R21AI166861-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10353468. Licensed CC0.

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