Recurrent airway obstruction (RAO, also called heaves) appears to have a genetic basis, but that genetic basis isn’t the same in all horses, Swiss researchers say. While the clinical signs can be the same, the disease's underlying genetic mechanisms can vary from one horse family to another.
What’s more, those genetic mechanisms are causing an immune response in the whole body, not just in the lung itself, said Simone Lanz, doctoral student and resident of the Swiss Institute of Equine Medicine at the University of Bern.
On a cellular level, there are significant differences between different RAO-affected horse families with different genetic bases, said Lanz. She and colleagues made this discovery by evaluating cytokines—proteins involved in activating immune responses which are expressed (produced and released) by special whole-body immune cells called peripheral blood mononuclear cells (PBMCs).
Based on the genetic background of the family, PBMCs react very differently with their cytokine expressions when exposed to various extracts, Lanz said, including exposure to hay dust, strongylids (nematode intestinal worms) parasite-related stimuli, and other allergens.
In her study Lanz and colleagues investigated two Swiss Warmblood family groups (half-brothers and half-sisters produced by a same sire) that had a tendency to develop RAO. Both stallions that sired these two groups were diagnosed with RAO, she said.
The signs of disease—including rapid breathing, difficulty breathing, and excessive mucus production—were identical regardless of genetic background, said Lanz. However, the difference between these two families was where the RAO genetic coding occurred in their DNA.
In the first family, the genetic coding for RAO was recessive, and it was located on Chromosome 13. Previous studies had already shown that this first family also had increased parasite resistance against strongylids. Meanwhile, the second family had a dominant genetic code for the disease on Chromosome 15. This second family had no particular parasite resistance.
“Using PBMCs (and not cells from the lung, for instance) we were able to show that the genetic determinants of RAO are involved in a systemic ('whole body,' as opposed to local lung) response to RAO- and to strongylid parasite-related stimuli,” Lanz said.
Next, researchers looked at both the RAO-positive horses (n=17) and healthy horses (n=14) from both family groups. The team stimulated PBMCs from all the horses for 24 hours with hay dust extracts—which appear to be related to RAO onset—strongylid parasite stimuli, and other potential allergens. The researchers then looked at how messenger RNA (mRNA) was expressed from a specific set of cytokines—mainly the interleukin 4R (IL-4R) gene in the first family’s Chromosome 13, since other studies have already shown a link between this gene and RAO in that family.
The hay dust extract caused significantly more cytokine mRNA activity in the IL-4R gene in RAO-positive horses in the first family, but not the second family, Lanz said. Another allergen, cyathostomin extract (a mixture of small strongylid parasites), caused similar results. Furthermore, hay dust extract caused significantly more mRNA activity of another interleukin gene, the IL-10 gene, in RAO-positive horses in the first family, but not in the second family. This confirmed that not only is RAO a systemic disease, but its mechanisms of action are also dependent on its genetic basis, she said.
“The more we know about a disease (and in this case about the genetic background), the better the understanding for the whole condition,” Lanz said. “Ultimately we hope to then be able to make better recommendations to horse owners.”
In the meantime, owners can now understand that heaves aren’t just a lung problem; they’re a whole-body issue involving the immune system. And while heaves have a genetic basis, it’s not the same genes in all horse families. Researchers are honing in on what leads to the disease that will help owners make better treatment decisions and better breeding selection.
The study, "Effect of hay dust extract and cyathostomin antigen stimulation on cytokine expression by PBMC in horses with recurrent airway obstruction," was published in Veterinary Immunology and Immunopathology.
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