Researchers found the immune marker associated with a tick-linked red meat allergy in a surprisingly large share of blood donations from several US states, according to a study published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
The marker is an IgE antibody that targets galactose-α-1,3-galactose, better known as alpha-gal. That sugar molecule is found on cells from nonprimate mammals, including cattle and pigs. It also appears in tick saliva, especially from the lone star tick, Amblyomma americanum. After a tick bite, some people develop alpha-gal IgE antibodies. Some of them then react to red meat or other mammal-derived products such as dairy or gelatin.
The new data do not mean that nearly a third of people in some states have alpha-gal syndrome. That distinction is the whole point, and it is where a lot of sloppy medicine can start. A positive antibody test can show sensitization. It does not, by itself, prove the person gets sick after eating meat.
The CDC has previously estimated that alpha-gal syndrome affects about 0.14% of the US population, or up to 450,000 people. The antibody estimates in the new study are much higher in places where lone star ticks are established, suggesting that asymptomatic sensitization may be common while diagnosed illness remains far less common.
What the study measured
A research team led by infectious disease specialists at the University of North Carolina at Chapel Hill tested 3,000 blood donation samples from 10 states, with 300 samples from each state. The researchers then used those results to estimate how common alpha-gal IgE antibodies may be in the broader population.
Six of the states are within established lone star tick territory: Arkansas, Kentucky, Missouri, South Carolina, Tennessee and Virginia. Maine and Minnesota include areas where the tick may be present. New Mexico and Washington are outside the tick’s known range.
The highest estimates came from states in lone star tick territory. South Carolina had the lowest estimate among those six states, at 5.5%. The other five ranged from 21.5% in Tennessee to 31.2% in Arkansas. Taken together, those five states had an estimated prevalence of 24%.
Maine and Minnesota came in at 10.6% and 5.4%, respectively. New Mexico and Washington had the lowest estimates, at 1.9% and 1.1%.
A delayed allergy, and a messy diagnosis
Alpha-gal syndrome is awkward to diagnose because reactions often begin two to six hours after a meal. People may not connect a late-night episode of hives, vomiting, diarrhea or breathing trouble with a burger eaten hours earlier. Severe reactions can include anaphylaxis, with throat tightening, swelling of the lips or tongue, dizziness, weak pulse and falling blood pressure.
The syndrome was first described in the early 2000s, and researchers still do not know why some people make alpha-gal IgE antibodies after tick bites while others do not. They also do not know why some antibody-positive people can eat meat without obvious symptoms.
That problem showed up early in work on cetuximab, a monoclonal antibody cancer drug that contains alpha-gal. Researchers reported in 2007 that some cancer patients in Tennessee and North Carolina had severe allergic reactions to cetuximab. Those patients had alpha-gal IgE antibodies, but they did not report trouble eating meat.
The MMWR researchers said clinicians should not diagnose alpha-gal syndrome based on the antibody test alone. The CDC’s case definition requires symptoms after exposure to red meat or other relevant mammal-derived products. Clinical guidelines also recommend a trial period of avoiding meat to see whether symptoms improve before confirming the diagnosis.
Several questions remain open. The researchers do not know what share of people with alpha-gal IgE antibodies have, or later develop, alpha-gal syndrome. They also note that small studies have linked alpha-gal IgE antibodies with higher risk of coronary artery disease, though that finding needs more work. For now, the surveillance data mostly show where researchers should look harder, and where a blood test without clinical context can make a mess.
This story draws on original reporting from Ars Technica.
