Early exposure curbed allergies in Icelandic horses

Horses exposed early in life to an allergen were less likely to react when exposed again later in life, according to a new study of Icelandic horses at Cornell that has implications for human allergies.

Horses that were exposed at birth to a midge that can cause an extreme skin allergy never succumbed to the condition, while 62.5% of horses that were first introduced to the midges in adulthood developed an itchy eczema-like reaction, the 13-year study found.

The results, published on Oct. 21in Frontiers in Immunology, were only possible because these midges, called Culicoides, don't exist in Iceland, allowing the researchers to test their theories on naïve horses, as well as offspring whose exposures to the allergen varied in timing.

The findings support the idea that early exposure to an allergen can prime an individual's immune system to tolerate it and not become allergic later in life.

Since the horse's immune systems has many similarities to humans, the study corroborates related findings in humans, including the hygiene hypothesis, which is based on the observation that children who grew up on farms with multiple animal and environmental exposures developed far fewer allergies than children raised in clean, more sterile homes.

"Training of the immune system to develop tolerance against allergens early in life creates a specific ability to adjust to those allergens and recognize them as harmless," said Dr. Bettina Wagner, the James Law Professor of Immunology at the College of Veterinary Medicine. "The earlier it happens, the more successful it is."

Elisabeth Simonin, a postdoctoral researcher in Wagner's lab, is the paper's first author.

The study focuses on hypersensitivity to the bite of Culicoides midges, which are found in many parts of the world, but not Iceland. Female midges suck blood as part of their reproductive cycle, injecting anti-coagulant proteins when they bite that can elicit an allergic response on horses. Symptoms manifest as dermatitis, extreme itchiness and hair loss, with severe cases leading to weight loss.

Icelandic horses, often bred in Iceland and exported elsewhere as adults, have been particularly susceptible to the allergic reaction. As a doctoral student, Wagner had heard a rumor about the horses. "And the rumor was, if you export an adult horse from Iceland, they more often get a severe allergic reaction to Culicoides," Wagner said. "But when the horses are bred in Europe, disease incidence is much, much lower."

Since then, epidemiological studies have confirmed that the rumors were true. The current study sought to address why this pattern occurs, by asking whether early exposure and maternal immunity might be playing roles.

In the study, three cohorts of horses, all housed at Cornell, differed by the timing of their exposures to Culicoides and whether their mothers carried and transferred allergy-specific maternal antibodies. Observations and human studies have suggested that a type of immune system antibody involved in allergic reactions called Immunoglobulin E (IgE) could get transferred from an allergic mother to newborns, leading to higher rates of allergy.

Along with finding high rates of allergy when Culicoides exposure first occurred in adulthood, and no hypersensitivity when foals were exposed their entire lives, a moderate allergy rate (21.4%) was found when foals were first introduced to allergens in adolescence. Also, no influence on rates of allergy development was found for foals born to mothers who had been exposed to Culicoides and carried IgE antibodies to the allergens.

Co-authors include Sigurbjorq Torsteinsdottir, Vilhjalmur Svansson and Sigriour Bjornsdottir, all at the University of Iceland in Reykjavik; Heather Freer, a laboratory technician in Wagner's lab; and Justine Tarsillo, DVM '25.

Funding for the importation of horses and the maintenance of the Icelandic herd at Cornell was provided by the Harry M. Zweig Memorial Fund for Equine Research at Cornell University.