In some parts of the US, up to 30 percent of people may carry the antibody behind a red meat allergy spurred by tick bites, far exceeding the estimated number of people who actually have the allergy, according a study published in Morbidity and Mortality Weekly Report.
The findings suggest far more Americans than previously thought may be at risk of the allergy, which can make having a hamburger for dinner a potentially life-threatening choice. The Centers for Disease Control and Prevention has previously estimated that only 0.14 percent of the US population (up to 450,000 people) has the allergy. But the study also highlights how little we understand about this unique disease—and the challenges of accurately diagnosing it.
The study surveyed blood donations for the disease’s key antibody, which is in a class dubbed IgE and specifically attacks a double-sugar molecule called galactose-α-1,3-galactose, also known as alpha-gal. This disaccharide is found decorating the cells of nonprimate mammals, including cows and pigs, but it’s also released in the saliva of ticks, particularly the lone star tick (Amblyomma americanum). People bitten by ticks can develop IgE antibodies against alpha-gal, which can sometimes go on to trigger the allergic response to eating red meat as well as other animal products, such as dairy and gelatin.
The allergy, called alpha-gal syndrome, is notorious for its delayed onset, flaring between two and six hours after a meal—making it difficult for people to connect the reaction to food. Symptoms can include hives, nausea, vomiting, abdominal cramps, diarrhea, and/or signs of a severe allergic response called anaphylaxis, which can be marked by trouble breathing, throat tightening, swelling tongue or lips, dizziness, weak pulse, and a drop in blood pressure.
Alpha-gal syndrome was only first described in the early 2000s, and researchers still have a slew of questions about it, including why some people develop alpha-gal IgE antibodies and why only some of those who have the antibody seem to have the allergy.
Early on, researchers realized there were people with so-called asymptomatic sensitization to alpha-gal. In other words, there are people with the antibody against the carbohydrate who don’t seem to have an allergic response to meat. This became clear in 2007 when researchers reported that many cancer patients were having severe allergic reactions to a cancer treatment called cetuximab—a monoclonal antibody drug that just happened to contain alpha-gal. The allergic response was first noticed when cetuximab was used in patients from Tennessee and North Carolina, where there are established populations of the lone star tick. While the cancer patients had alpha-gal IgE antibodies and the same allergic reaction to the drug as seen with alpha-gal syndrome, the cancer patients didn’t report problems eating meat.
New estimates
To date, researchers still don’t know how common it is to have alpha-gal antibodies, hence the new MMWR study. A group of researchers, led by infectious disease experts at the University of North Carolina at Chapel Hill, collected samples from 3,000 blood donations across 10 states, with 300 samples per state. They tested the samples for the antibody and used the data to make population-level estimates for the antibody’s prevalence.
Six of the states were firmly in lone star tick territory: Arkansas, Kentucky, Missouri, South Carolina, Tennessee, and Virginia. There were also two states out of the tick’s range, New Mexico and Washington, and two states with regions that may have the ticks, Minnesota and Maine.
The researchers found, as expected, that alpha-gal antibodies were most common in the states with the lone star tick. Of the six states in the tick’s territory, South Carolina had the lowest estimated prevalence of 5.5 percent. The other five ranged from 21.5 percent (Tennessee) to 31.2 percent (Arkansas). Collectively, the five top states had a prevalence estimate of 24 percent. The two states that only had some regions estimated to be in range for the tick, Maine and Minnesota, had prevalence estimates of 10.6 percent and 5.4 percent, respectively. Estimates for New Mexico and Washington, outside the tick’s range, were lowest, at 1.9 percent and 1.1 percent, respectively.
The researchers did not have data from the blood donors to know if they had been diagnosed with alpha-gal syndrome or not. But, the prevalence in the donors and the modeled population-level estimates far exceed the estimated number of people with alpha-gal syndrome. The results suggest asymptomatic sensitization to alpha-gal may be common, while alpha-gal syndrome is not, the researchers conclude. This poses a risk for alpha-gal syndrome to be over diagnosed and for patients to unnecessarily restrict their diets if clinicians rely solely on the antibody’s presence. The researchers stress that a diagnosis should only be given if people report symptoms after meals with red meat. Clinical guidelines recommend that people suspected of alpha-gal syndrome do a trial period of avoiding meat to see if symptoms improve before getting a diagnosis.
On the other hand, researchers still don’t know what proportion of people with antibodies have alpha-gal syndrome or are at risk of developing it later, possibly after additional tick bites. It’s also unclear if having alpha-gal IgE antibodies poses other risks. For instance, some small studies have linked alpha-gal IgE antibodies to higher risks of coronary artery disease.
The researchers behind the new study suggest such alpha-gal antibody surveillance data can help identify areas with high prevalence ripe for further research.
