ORLANDO — Patients whose red blood cells express the B antigen appear to be protected from the alpha-gal — or red meat — allergy, new research shows.

Jonathan Brestoff

"Red meat allergy is a recently recognized allergic reaction to galactose-a-1,3-galactose," said Jonathan Brestoff, MD, PhD, from the Washington University School of Medicine in Saint Louis, Missouri. "Our study shows that those who have blood types B or AB are at decreased risk of developing alpha-gal-mediated red meat allergy, compared with patients who have blood types O or A."

"Our recommendation is that all people who are being evaluated for red meat allergy should have their blood type determined early in their work-up," Brestoff said here at the American Academy of Allergy, Asthma and Immunology and World Allergy Organization 2018 Joint Congress.

Our recommendation is that all people who are being evaluated for red meat allergy should have their blood type determined early in their work-up.

"Red meat allergy was described as early as 2009," but experts believe that the allergy is not new, he explained. Although its prevalence is not known, it is more common in the southeastern United States than in other regions of the country, he pointed out.

"The disease is thought to be caused by tick bites — namely, the lone star tick — but there may be other species that are responsible also," he added. "The current thinking is that ticks are carried by wildlife and pets that can get a blood meal and, in the process, acquire the alpha-gal antigen."

The local allergic reaction that occurs after a tick bites a human can lead to sensitization to alpha-gal, which can lead to a susceptibility to meats that contain alpha-gal, such as steak and pork.

Many patients go years before they are diagnosed because "the actual symptoms of red meat allergy don't appear until 4 to 6 hours after ingestion, which is very unusual for a food allergy. Usually a reaction occurs within 30 minutes to an hour," Brestoff said. A patient can go out for a steak dinner, go to bed, and then wake up in the middle of the night with anaphylaxis.

Because the B antigen that determines blood type as A or AB looks similar on a molecular level to alpha-gal, Brestoff and his colleagues hypothesized that patients who have the B antigen have immune systems that are trained to ignore things that look like alpha-gal, so are not as susceptible to the meat allergy.

The B Antigen

To test their theory, the team assessed blood types in 592 patients with red meat allergy and 92 control subjects.

They expected that the frequency of B or AB blood types would be about 20%, but it was only 4.35% in those with the allergy.

Patients expressing the B antigen were less likely than patients not expressing the B antigen to produce alpha-gal-specific immunoglobulin (Ig) E (odds ratio [OR], 0.19; P = .023) and beef-specific IgE (OR, 0.29; P = .016), and were five times less likely to have a red meat allergy (OR, 0.20; P = .004).

Another study presented at the meeting showed that patients with red meat allergy might be five times more likely to be allergic to insect stings.

More Susceptible to Insect Allergy?

Maya Jerath

"With tick populations expanding, red meat allergy is becoming more prominent," said Maya Jerath, MD, PhD, from the University of North Carolina at Chapel Hill.

Jerath and her colleagues tested the blood of 109 patients with red meat allergy and 26 control subjects for sensitization to five stinging insects: honey bee, white-faced hornet, common wasp, paper wasp, and fire ant.

The rate of allergic sensitization was five times higher in the allergic group than in the control group. "This gives support to what we have seen in the clinic," Jerath said.

This finding points to shared immunologic factors that make people with red meat allergy "more susceptible to insect allergy," she told Medscape Medical News. "And it supports the notion that some people have a stronger tendency to develop allergic sensitization to an allergen that is delivered through the skin, either from a tick bite or a sting from an insect."

Both Brestoff and Jerath stressed the importance of increased awareness of this association.

"It would be useful for patients and practitioners to know about this association, and for healthcare providers to ask alpha-gal patients whether or not they have had adverse reactions to stinging insects," Jerath said.

"In talking to my patients, a very large number of them report that they have had symptoms for 20 or 30 years. I believe that this allergy has been around for a very long time, and that we are just becoming more aware of it," she explained. "In the past, when a patient would come to me with red meat allergy, I didn't know what it was and would just give a diagnosis of idiopathic anaphylaxis."

"The patients who are being diagnosed currently have very severe, very clear-cut reactions," Brestoff pointed out. "I wonder if there are people out there who don't react all the time and have more subtle symptoms that they just don't associate it with food exposure."

He added, "It's just going to take more awareness, among physicians and patients alike, to really pick up the diagnosis."

The lore around our clinic is that senior physicians used to tell the trainees, 'there's a certain group of patients who are going to tell you that they're allergic to red meat. We don't know what it is, we don't know how to test for it, but just believe them'.

Cosby Stone Jr

These studies are "really interesting," said Cosby Stone Jr, MD, from Vanderbilt University in Nashville, Tennessee.

"We know that alpha-gal is similar in its structure to blood group antigens that determine blood type," he told Medscape Medical News.

"These findings are similar to those that have been shown in Europe, where the B blood group seems to be protective against alpha-gal because it's structurally similar to alpha-gal," he noted.

"When you are exposed to it through a tick bite, you're not going to develop an allergy to it because it's like your own blood group. This is one of the first hints that there's a genetic predisposition for certain people to get alpha-gal," Stone said.

"The lore around our clinic is that senior physicians used to tell the trainees, 'there's a certain group of patients who are going to tell you that they're allergic to red meat. We don't know what it is, we don't know how to test for it, but just believe them'," he reported.

People with red meat allergy often are allergic to vaccines, medications, and other things, he added.

"It's the same allergy, but presents in a lot of different flavors. People will often go through life having allergies to different things, never realizing that the common factor is alpha-gal," Stone said.

"It's like science fiction. You could be walking through the woods and a tick, which just fed on a cow or a deer, would bite you and inject a little bit of that blood into your system, and you would develop an allergy to that blood, the sugar in that blood, and have allergic reactions to medications and meat. It's a bizarre story, but it turns out to be true," he said.

Brestoff's study was funded by Washington University. Jeraf's study was funded by University of North Carolina at Chapel Hill. Brestoff, Jerath, and Stone have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma and Immunology (AAAAI) and World Allergy Organization (WAO) 2018 Joint Congress: Abstract 627, presented March 3, 2018; Abstract 721, presented March 5, 2018.

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