Scientists at the University of Virginia have seemingly come closer to unravelling the mystery behind a strange red meat allergy caused by certain tick bites. They report finding a way to trigger the allergy in lab mice — an important step for studying the condition. And with the help of animal experiments, they also claim to have identified important changes to the immune system that might be caused by these bites.
Red meat allergy is what happens when people become hyper-sensitised to the sugar alpha-gal, which is abundantly produced by most mammals but not primates (like us). Its symptoms are much like the typical food allergy, with hives and swelling being common. Like other food allergies, these reactions can also be life-threatening and merit immediate medical treatment.
Red meat allergic reactions are usually delayed for hours after a meal, though, compared to the near-instantaneous reactions normally seen. And unlike other food allergies, the condition is predominantly, if not exclusively, caused by the bite of certain ticks. In the U.S., the leading culprit has been the Lone Star tick, which is common throughout the eastern, southeastern and south-central states, but other tick species in other countries have been linked to the allergy as well.
At this point, there are still more questions than answers about red meat allergy. While the condition is likely rare, for instance, we don’t really know how often it occurs, nor the chances for any single bite to turn someone allergic. Most importantly, we don’t know how these bites spark the allergy in the first place. Everyone has antibodies to alpha-gal, for example, but most of us don’t have the specific sort of immune reaction to meat — led by a type of antibody called IgE — that characterises the condition.
Animal models are often a crucial early step to studying any disease or disorder found in people. And that’s what the authors of the new study, published in the Journal of Immunology, say they’ve managed to pull off. But it wasn’t exactly easy, according to senior author and UVA researcher Loren Erickson, since mice naturally produce alpha gal. That means they don’t typically have a immune response to it at all.
“Thus, our study used mice that are deficient in the gene that makes alpha-gal, which mirrors humans that also lack the gene that makes alpha-gal,” he told Gizmodo.
In these alpha-gal deficient mice, they were then able to create the same IgE allergic reaction to eating meat seen in people with the condition. And as with people, they induced the allergy by exposing the skin of their mice to proteins found in Lone Star ticks.
Previous researchers have claimed to create mice models for studying red meat allergy. But Erickson says his team’s work is likely the first published research of a clinically relevant model, one that let the team study the immune responses of these allergic mice in “real time.” That’s something that would be much harder to do with people.
“One of the outstanding questions in the field is what is it about the tick bite, or the tick itself, that induces an immune response to alpha-gal,” Erickson said. “This model could be used to figure out what chemicals/compounds in the tick trigger an immune response.”
The model could also help researchers understand the way these chemicals are causing the immune system to become hypersensitive to alpha-gal.
In their early mice experiments, for example, the team found evidence that a specific type of immune cell, called a CD4+ T cell, played a key role in the immune overreaction to alpha-gal, both during the initial tick exposure and when the mice ate meat afterward.
Other research by the authors has found that another type of immune cell, called a B-cell, is commonly found in high levels among people with red meat allergy. And when the team created mice whose B-cells couldn’t produce a protein called MyD88, the mice no longer produced IgE in response to the ticks. MyD88 is thought to help immune cells communicate with the outside world through certain signalling pathways.
Knocking out MyD88 in people to prevent red meat allergy isn’t exactly feasible or even practical (people genetically deficient in it are much more likely to develop severe bacterial infections, for one). But the findings provide new clues for researchers like Erickson and his team to track down — clues that might one day uncover a possible treatment or way to prevent it. Currently, while some people with the condition do report being able to eat meat without incident after a certain time, others may have to live with the allergy forever.
The team next plans to look more closely at which types of immune cells are most responsible for creating the IgE antibodies that make us allergic to red meat, as well as how the whole process gets started.
“If we can identify what these immune mechanisms are, then it provides an opportunity to develop therapeutic strategies to prevent the generation of IgE antibodies to alpha-gal,” Erickson said.