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The Mystery Meat Allergy: You Don’t Hate Ticks Enough?

Maya Jerath and Scott Commins

UNC colleagues Maya Jerath and Scott Commins are working to characterize the tick-borne meat allergy, alpha-gal. (Photo by Anna Routh Barzin ’07)

When Melody Adams ’85 woke up covered in an itchy rash, her husband grabbed the Benadryl and Adams jumped in the shower, thinking, “I bet it was those weird Asian spices I ate.” But the hives reappeared a week later. Then it happened again, and again, and again, always in the middle of the night.

One day, a rare midday trip to a fast-food joint at the mall caused her to break out in hives around dinnertime, with the added bonus of vomiting.

“That’s when I thought it was the red meat,” Adams remembered.

At a friend’s birthday party, she struck up a conversation with another guest — Scott Commins, an allergist and researcher at UNC’s Thurston Arthritis Research Center. Commins told her he specializes in a weird tick-borne meat allergy called alpha-gal.

“I think I have that!” Adams blurted.

A week later, Commins ran a simple blood test — a test he helped develop — to confirm she was now allergic to a sugar in red meat and pork called alpha-gal, which is short for galactose-alpha-1,3-galactose. This sugar is not in poultry, fish or, importantly, in humans.

Typically, when we eat meat, antibodies in our digestive tract recognize alpha-gal — and all sugars, fats and proteins in food — but the antibodies do not trigger allergic reactions. These antibodies fall into two classes of immunoglobulins.

But people allergic to meat have different antibodies that can cause a violent immune response to alpha-gal. This involves a third class of immunoglobulins (call it IgE), which go haywire in the presence of alpha-gal, causing symptoms that include abdominal pain, diarrhea, vomiting, hives, itchy hands, trouble swallowing and anaphylactic shock — the medical emergency that requires a 911 call or epinephrine.

Commins and a UNC colleague, Maya Jerath, are conducting research to characterize this relatively new phenomenon, determine the pathology and hopefully develop treatments. They are two of the few researchers in the U.S. working on this strange allergy they simply refer to as alpha-gal. And it turns out the culprit that causes people such as Adams to conjure up these antibodies is our summertime arch-nemesis, the tick.

“To be honest, we can’t say for sure exactly how ticks cause the allergy,” Commins said. “But we think we know, and we’re trying to prove it.”

Commins’ and Jerath’s working hypothesis is that a tick bites an animal, such as a dog, cow, cat, pig or deer, and then falls off. The tick has alpha-gal in its saliva from the blood meal. Then it bites a human, injecting alpha-gal under the person’s skin. This alpha-gal enters a lymph node and triggers the creation of the IgE antibodies. These antibodies become soldiers-in-waiting throughout the body, including the digestive tract. When this person eats meat, alpha-gal binds to the specific IgE antibodies, triggering an allergic reaction.

Unfortunately, the allergy is not so easy to recognize as an allergy. Symptoms don’t appear until three to six hours after a meal. Sometimes, a person eats meat and nothing happens. But the next time the person eats meat, he or she can break out in hives. Some people have severe gut discomfort. People don’t typically associate that with an allergy.

“I suspect there are a lot of undiagnosed people,” Commins said. “They might go to a GI specialist and be diagnosed with irritable bowel syndrome, which is a sort of catch-all diagnosis. But in reality, some of these people are probably allergic to alpha-gal.”

It’s the hives or trouble breathing that clue people in to a potential allergy. Even then — say you land in the ER due to a swollen airway or because you passed out — it’s tough to pin down the cause as a meat allergy.

Commins has one patient who, before she came to him, went on a horrific diagnostic odyssey, including removal of her gall bladder and part of her pancreas. Doctors gave her pancreatic enzymes derived from pigs. This made her worse. She couldn’t eat. Doctors inserted a feeding tube to keep her alive. Then she read about Commins’ work, and he diagnosed her with alpha-gal. She’s on the mend now.

In 2009, Commins was at the University of Virginia, where he and another researcher documented the first 24 cases of alpha-gal in the U.S. Today, there are thousands of documented cases. Most of these people live in the South — from Missouri and Arkansas, eastward toward Virginia and points south. The Lone Star Tick is suspected to be the main culprit, but Commins thinks other tick types and arthropods, such as chiggers, shouldn’t be ruled out.

Commins now runs his own lab at UNC and is studying how alpha-gal does what it does. His colleagues are using a line of mice for which they’ve knocked out the gene that creates the alpha-gal sugar.

His lab then injects ground-up tick saliva glands under the skin of mice to mimic a tick bite. (They also can use actual ticks that bite the mice, but keeping many live ticks in an animal facility isn’t the best idea.)

The experiments include figuring out which immune system cells and substances are important for this allergic reaction. Once they pinpoint the underlying molecular causes of the allergy, they can start thinking about possible treatments.

Commins and Jareth also are working on the natural history of alpha-gal. Some people react violently to all meat that contains alpha-gal. Other people, such as Melody Adams, can eat pork but not red meat. Commins and Jareth want to know why.

According to their data, the alpha-gal allergy may not be permanent, at least not for all people.

“In our patients, we’ve found that IgE antibody levels decrease substantially over time, if there are no further tick bites,” Commins said. After about two years, some people should be able to eat meat again.

Adams is a gardener who spends a lot of time outdoors and is married to Chapel Hill burger baron Al Bowers ’88, who owns Al’s Burger Shack; they recently opened a restaurant bearing her name, the short-lived Mel’s Commissary and Luncheonette. But the burgers? She isn’t sure she wants to test those waters again.

“I think I’m good, thanks,” she said.

— Mark Derewicz 


 

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