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Frontiers in immunology2025; 16; 1654693; doi: 10.3389/fimmu.2025.1654693

Early allergen introduction overrides allergy predisposition in offspring of horses with Culicoides hypersensitivity.

Abstract: The origins of allergy are both genetic and environmental. We performed a full-sibling study to determine the role of early-in-life or delayed allergen introduction on hypersensitivity development in a cohort with history of an allergic phenotype and Culicoides hypersensitivity. IgE-mediated allergies naturally develop in many mammalian species, and we used a horse model of allergy called hypersensitivity. hypersensitivity is a seasonal, recurrent, IgE-mediated allergy caused by the salivary proteins of biting midges. Unassigned: The study included four cohorts that lived together in the same environment, only differing in the timing of allergen exposure and the transfer of allergen-specific maternal antibodies. The parent cohort was first exposed to allergens in adulthood, and each full-sibling cohort was first exposed to allergen either in puberty or at birth. All full-siblings had at least one allergic parent with an allergic phenotype, suggesting a predisposition to develop allergy. Allergen-specific IgE and IgG isotypes were measured before and after exposure to to determine whether maternal-acquired allergen-specific antibodies influenced the rate of hypersensitivity development. All four cohorts were followed for at least nine years of allergen exposure. Unassigned: The rate of allergy development was inversely related to the timing of allergen exposure where introduction in adulthood led to the highest rate of allergy development (62.5%), a moderate allergy rate was found for introduction during adolescence (21.4%), and no individuals exposed at birth developed hypersensitivity. In addition, exposure to maternally-acquired allergen-specific IgE and IgG did not influence the rate of allergy development in the cohorts exposed to allergen at birth. Unassigned: We provide strong evidence in a full-sibling study that early-in-life allergen exposure, independent of maternal allergen-specific immunoglobulin, prevents hypersensitivity development in individuals born to parents with an allergic phenotype.
Copyright © 2025 Simonin, Torsteinsdóttir, Svansson, Björnsdóttir, Freer, Tarsillo and Wagner.
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Publication Date: 2025-10-21 PubMed ID: 41194920PubMed Central: PMC12583015DOI: 10.3389/fimmu.2025.1654693Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This research investigates how the timing of allergen introduction influences the development of IgE-mediated allergies, specifically Culicoides hypersensitivity, in horses genetically predisposed to allergy due to parental allergic phenotypes.
  • The study finds that early-life exposure to allergens can prevent the development of allergy, even in offspring with genetic susceptibility, and that maternal allergen-specific antibodies do not significantly affect allergy development.

Background

  • Allergic diseases can be influenced by both genetic factors and environmental exposures.
  • Culicoides hypersensitivity is an IgE-mediated seasonal allergy seen in horses, caused by bites from Culicoides midges.
  • This allergy serves as a model for studying IgE-mediated hypersensitivity in mammals.
  • There is interest in whether the timing of allergen exposure in life affects the likelihood of developing allergy, particularly in individuals who have a genetic predisposition.

Study Design

  • The study used a full-sibling design, where sibling horses shared at least one allergic parent, suggesting a genetic predisposition to allergy.
  • Four cohorts of horses were closely studied; they all lived in the same environmental conditions but differed in the timing of their initial allergen exposure:
    • Parent cohort: first exposed to allergens in adulthood
    • Two full-sibling cohorts: first exposed during puberty
    • One full-sibling cohort: first exposed at birth
  • The cohorts also varied in whether they received maternally transferred allergen-specific IgE and IgG antibodies to assess if maternal antibodies influenced allergy development.
  • Allergen-specific IgE and IgG antibody levels were measured before and after exposure to Culicoides allergens to monitor the immune response.
  • The cohorts were followed for a long term — at least nine years — to track allergic outcomes.

Key Findings

  • The timing of allergen exposure had a significant inverse relationship with the rate of allergy development:
    • Delayed exposure, i.e., introduced in adulthood, had the highest allergy rate of 62.5%.
    • Exposure during puberty showed a moderate allergy rate (21.4%).
    • Exposure starting at birth resulted in zero horses developing Culicoides hypersensitivity.
  • Exposure to maternal allergen-specific IgE and IgG antibodies did not influence allergy development in the cohort exposed from birth, indicating maternal antibodies were not a protective or driving factor.

Conclusions and Implications

  • The study strongly supports the concept that early-life exposure to allergens can override inherited genetic predisposition to allergy.
  • Preventing allergy by early allergen introduction may be independent of maternal antibodies, indicating the timing of exposure is a critical window for immunological tolerance.
  • This finding may have broader implications for understanding allergy prevention strategies in other species, including humans.

Additional Notes

  • The use of a natural and well-characterized mammalian allergy model (horses with Culicoides hypersensitivity) strengthens the relevance of the findings to naturally occurring IgE-mediated allergies.
  • Long-term follow-up enhances confidence in the durability of protection conferred by early allergen exposure.

Cite This Article

APA
Simonin EM, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Freer H, Tarsillo J, Wagner B. (2025). Early allergen introduction overrides allergy predisposition in offspring of horses with Culicoides hypersensitivity. Front Immunol, 16, 1654693. https://doi.org/10.3389/fimmu.2025.1654693

Publication

Frontiers in immunology
ISSN: 1664-3224
NlmUniqueID: 101560960
Country: Switzerland
Language: English
Volume: 16
Pages: 1654693
PII: 1654693

Researcher Affiliations

Simonin, Elisabeth M
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Torsteinsdóttir, Sigurbjorg
  • The Institute for Experimental Pathology, at Keldur, University of Iceland, Reykjavik, Iceland.
Svansson, Vilhjálmur
  • The Institute for Experimental Pathology, at Keldur, University of Iceland, Reykjavik, Iceland.
Björnsdóttir, Sigríður
  • Office of Animal Health and Welfare, Icelandic Food, and Veterinary Authority, MAST (MAST), Selfoss, Iceland.
Freer, Heather
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Tarsillo, Justine
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.

MeSH Terms

  • Animals
  • Ceratopogonidae / immunology
  • Horses / immunology
  • Allergens / immunology
  • Female
  • Immunoglobulin E / immunology
  • Immunoglobulin E / blood
  • Hypersensitivity / immunology
  • Hypersensitivity / veterinary
  • Male
  • Horse Diseases / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / blood
  • Insect Proteins / immunology
  • Disease Susceptibility
  • Immunity, Maternally-Acquired

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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