Immunologic comparison of alpha-gal sensitized and non-sensitized groups from a community based sample
- 1Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina , , ,
- 2Allergy & Immunology School of Medicine, University of North Carolina , , ,
Abstract
Introduction: Alpha-gal syndrome is delayed, IgE-mediated hypersensitivity reaction to galactose-α-1, 3-galactose (alpha-gal), a carbohydrate epitope found in non-primate mammals. Sensitization is typically triggered by tick bites, with some sensitized individuals progressing to severe allergic reactions to red meat and other alpha-gal containing substances. Despite increasing clinical recognition, the immunologic mechanisms underlying alpha-gal sensitization remain poorly defined. Therefore, this article aimed to identify whether there are distinct immunologic differences between sensitized and non-sensitized groups sampled from a well-characterized, community-based cohort.
Methods: Participants were matched by age, sex, and race/ethnicity then classified as sensitized (AG+) or non-sensitized (AG−) by laboratory criteria. Demographics, health history, and target concentration between the groups were compared using descriptive statistics, Wilcoxon tests, and multivariable logistic modeling.
Results: AG+ participants (n=50) showed elevated concentrations of innate immune markers including CD163, Chitinase-3-like 1, gp130, and MMP2 (all p < 0.0001), and reduced levels of regulatory cytokines including IL-10, IL-12p40, IL-35, LIGHT, and interferons IFNα2 and IFNβ. Logistic regression identified three independent cytokine predictors of alpha-gal sensitization: IL-1α (OR = 2.75, 95% CI: 1.40–5.41, p = 0.004), IL-35 (OR = 0.22, 95% CI: 0.10–0.49, p < 0.001) and LIGHT (OR = 0.19, 95% CI: 0.05–0.75, p = 0.02).
Discussion: Our findings showed distinct differences between AG+ and AG- groups, marked by increased pro-inflammatory signaling and decreased immune regulatory cytokines. These results support a model of immune dysregulation involving both the innate and adaptive arms of the immune system. Further research is needed to understand the functional role of these markers for those with clinical disease.
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BibTeX
@article{pickle2026immunologic,
title = {{Immunologic comparison of alpha-gal sensitized and non-sensitized groups from a community based sample}},
author = {Emily Owens Pickle and Kyndall Dye-Braumuller and Kia Zellars and Stella C.W. Self and Scott Commins and Melissa S. Nolan},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1824819},
url = {https://europepmc.org/article/PMC/PMC13663876},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immunologic comparison of alpha-gal sensitized and non-sensitized groups from a community based sample
AU - Emily Owens Pickle
AU - Kyndall Dye-Braumuller
AU - Kia Zellars
AU - Stella C.W. Self
AU - Scott Commins
AU - Melissa S. Nolan
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1824819
UR - https://europepmc.org/article/PMC/PMC13663876
AB - Introduction: Alpha-gal syndrome is delayed, IgE-mediated hypersensitivity reaction to galactose-α-1, 3-galactose (alpha-gal), a carbohydrate epitope found in non-primate mammals. Sensitization is typically triggered by tick bites, with some sensitized individuals progressing to severe allergic reactions to red meat and other alpha-gal containing substances. Despite increasing clinical recognition, the immunologic mechanisms underlying alpha-gal sensitization remain poorly defined. Therefore, this article aimed to identify whether there are distinct immunologic differences between sensitized and non-sensitized groups sampled from a well-characterized, community-based cohort. Methods: Participants were matched by age, sex, and race/ethnicity then classified as sensitized (AG+) or non-sensitized (AG−) by laboratory criteria. Demographics, health history, and target concentration between the groups were compared using descriptive statistics, Wilcoxon tests, and multivariable logistic modeling. Results: AG+ participants (n=50) showed elevated concentrations of innate immune markers including CD163, Chitinase-3-like 1, gp130, and MMP2 (all p < 0.0001), and reduced levels of regulatory cytokines including IL-10, IL-12p40, IL-35, LIGHT, and interferons IFNα2 and IFNβ. Logistic regression identified three independent cytokine predictors of alpha-gal sensitization: IL-1α (OR = 2.75, 95% CI: 1.40–5.41, p = 0.004), IL-35 (OR = 0.22, 95% CI: 0.10–0.49, p < 0.001) and LIGHT (OR = 0.19, 95% CI: 0.05–0.75, p = 0.02). Discussion: Our findings showed distinct differences between AG+ and AG- groups, marked by increased pro-inflammatory signaling and decreased immune regulatory cytokines. These results support a model of immune dysregulation involving both the innate and adaptive arms of the immune system. Further research is needed to understand the functional role of these markers for those with clinical disease.
SN - 1664-3224
ER -