# 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 · 2024 · $262,801

## Abstract

SUMMARY
Alzheimer’s disease (AD) is a leading cause of death among older adults. Its high prevalence, amounting to one
third of all seniors, warrants new research directions on the pathogenesis of AD that can unlock new treatments.
Studying AD in the context of emerging allergic diseases presents a key opportunity in this regard. Emerging
allergic diseases to food allergens present an important public health problem whose ramifications may extend
beyond the gastrointestinal tract to other organ systems, including the brain. This project capitalizes on
pioneering work by the study team on “alpha-gal syndrome” (AGS), by exploring how neuroinflammatory profiles
relate to tick-induced allergy to mammalian meat in patients sensitized to the carbohydrate allergen, galactose-
alpha-1,3-galactose (alpha-gal). The proposed work builds on the idea that tick bites promote systemic
inflammatory processes that could adversely impact the brain. This notion is bolstered by recent data, including
that of the study team, to support a link between sensitization to alpha-gal and cardiovascular disease. The
central hypothesis is that patients with IgE to alpha-gal develop inflammatory profiles that promote
neuroinflammation. Given that AGS is an antigen-driven disorder, we further posit that T cells are pivotal to this
process. The project leverages an extensive set of existing specimens and data from highly characterized
cohorts spanning the spectrum of sensitization to alpha-gal, as well as a unique comparison group of chronically
inflamed patients suffering from post-acute sequelae of severe COVID-19 illness. The approach in Aim 1A will
define neuroinflammatory states using an unsupervised integrative approach across hundreds of serum samples
from patients with alpha-gal sensitivity. This will include assaying canonical and candidate biomarkers of AD
using ultrasensitive assays, in conjunction with a broad set of cytokines and chemokines, and then defining
discrete inflammatory states using cluster analyses. Longitudinal assessments will be performed in a subsample
of 100 patients with IgE to alpha-gal who return for a follow up visit at 3-10 years after their initial visit, in order
to monitor the development of neuroinflammatory profiles in relation to change in IgE and decline in
neurocognitive function. Profiles will be validated using samples from patients with AD and in COVID-19 patients
with neurocognitive sequelae. In Aim 1B, deep T-cell profiling using spectral flow cytometry and machine
learning methods will be used to elucidate complex T-cell signatures that constitute “functional networks”
governing neuroinflammatory states that are defined in Aim 1A. Establishing a new paradigm for the
immunopathogenesis of AD will identify novel avenues for exploring the interaction between AD and allergic
disease, and ultimately aid in the design of new therapies for this devastating disease.

## Key facts

- **NIH application ID:** 10931183
- **Project number:** 3R37AI020565-40S2
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** THOMAS A. PLATTS-MILLS
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $262,801
- **Award type:** 3
- **Project period:** 1984-07-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931183

## Citation

> US National Institutes of Health, RePORTER application 10931183, IgE antibodies to the mammalian oligosaccharide galactose-alpha-1, 3-galactose (alpha-gal): immunology, epidemiology and relevance to allergic and inflammatory disease (3R37AI020565-40S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10931183. Licensed CC0.

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