Scientists at the University of Virginia seem to be getting close to solving the mystery behind a strange allergy to red meat caused by certain tick bites. They report finding a way to cause allergy in lab mice – an important step in studying the condition. And through animal experiments, they also claim to have found important changes in the immune system that can be caused by these bites.
Allergy to red meat is what happens when people become hypersensitive to sugar alpha-gal, which is richly produced by most mammals but not by primates (like us). Its symptoms are much like a typical food allergy, with nettle fever and swelling being common. Like other food allergies, these reactions can also be life-threatening and merit immediate medical treatment.
Allergic reactions to red meat are usually delayed by hours after eating, compared to the almost instantaneous reactions that are usually observed. And unlike other food allergies, the condition is predominantly, if not extremely, caused by the bite of certain ticks. In the US, the leading culprit is the Lone Star mite, which is common in the eastern, southeastern, and southwestern states, but other types of ticks in other countries are also allergic.
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At this point there are still more questions than answers about allergy to red meat. Although the condition is probably rare, for example, we don't really know how often it happens, or the chances of any one bite becoming allergic. Most importantly, we do not know how these bites ignite the allergy in the first place. Everyone has antibodies to alpha-gal, for example, but most of us do not have the specific type of immune response to meat – led by a type of antibody called IgE – that characterizes the condition.
Animal models are often a decisive early step in the study of any disease or disorder found in humans. And this is what the authors of the new study, published in the Journal of Immunology, say they were able to withdraw. But it wasn't easy, according to UVA senior author and researcher Lauren Erickson, because mice naturally produce alpha gal. This means that they have no immune response to it at all.
"In this way, our study uses mice that have a deficiency in the gene that makes alpha-gal, which mirrors people who also lack the gene that makes alpha-," he told Gizmodo.
In these alpha-gal-deficient mice, they were able to produce the same IgE allergic reaction to eating meat seen in people with the disease, and as in humans, they triggered the allergy by exposing the mice skin to proteins found in the ticks of the Lone Star.
Previous researchers claim to create mouse models for and learning about allergy to red meat. But Ericsson says the work of his team is probably the first published study of a clinically relevant model that allows the team to investigate the immune responses of these allergic mice in "real time."
"One of the unresolved questions in this area is what constitutes a tick bite or the tick itself that triggers an immune response to alpha-gal," says Erickson. "This model can be used to understand what chemicals / compounds in ticks that trigger an immune response."
The model can also help researchers understand how these chemicals cause the immune system to become hypersensitive alpha gal.
In their early experiments with mice, for example, the team found evidence that a specific type of immune cell, called a CD4 + T cell, plays a key role in the alpha-gal immune response, both during initial tick exposure and when mice eat meat afterwards.
Other studies by the authors found that another type of immune cell, called B-cell, is commonly found at high levels among people with allergies to red meat. And when the team created mice whose B cells could not produce a protein called MyD88, the mice no longer produced IgE in response to ticks. MyD88 is thought to help immune cells communicate with the outside world through specific signaling pathways.
Discarding MyD88 in humans to prevent red meat allergy is not exactly possible or even practical (people who have a genetic deficiency in it are much more likely to develop severe bacterial infections, for one). But the findings provide new clues for researchers like Ericsson and his team to discover – clues that may one day reveal a possible cure or a way to prevent it. At the moment, while some people with the condition report that they can eat meat without incident after a while, others may have to live with the allergy forever.
The following team plans to look more closely at which types of immune cells are most responsible for creating IgE antibodies that make us allergic to red meat, and how the whole process begins.
"If we can identify what these immune mechanisms are, then this allows us to develop therapeutic strategies to prevent the generation of IgE antibodies to alpha-gal," says Ericsson.