Epitope testing has been shown in studies to be far more reliable in diagnosing peanut allergy than traditional skin or blood testing. Now, new research reveals that epitope testing is also good at determining if a child with peanut allergy will react to trace amounts, or if they can consume one or more peanuts before starting to react.
The epitope test is the first to provide reaction “thresholds.” These may be useful for families in deciding how careful they need to be in avoiding peanuts. This includes whether their child can safely eat foods with the “may contain” warning.
The new test may also help families decide if they feel comfortable with trying an oral food challenge. As well, it may influence whether they want to pursue a desensitization treatment such as oral immunotherapy (OIT).
“We no longer have to look at everybody as being exactly the same when it comes to peanut allergy,” says Dr. Hugh Sampson, senior study author and a professor of pediatrics at the Icahn School of Medicine at Mount Sinai in New York City. The epitope threshold test, he says, “can dramatically cut down the anxiety of some people, knowing they could likely tolerate a certain amount of peanut without a problem.”
The study was published recently in Allergy. Epitope tests are available for order through the manufacturer, Allergenis, based in Hatfield, PA.
Amount of Peanut Before Person Reacts
Peanut allergies are stressful to manage, since reactions can be life-threatening. In some patients, consuming very small amounts of peanut will set off anaphylaxis. But for others, eating small amounts may not have much effect. Since traditional tests do not provide a way to know who will react to trace amounts, allergists simply advise strict avoidance of peanut for anyone who’s allergic.
Sometimes they will recommend an oral food challenge. That’s the gold standard allergy test, in which a patient consumes an allergenic food in gradually increasing amounts over several hours. The test confirms whether there’s an allergy and how much allergen will provoke a reaction. But oral food challenges are time-consuming and carry the risk of anaphylaxis. Often, families and allergists don’t want to take that chance with peanuts.
This is where epitope testing is changing allergy testing. Epitopes are sequences of amino acids that make up proteins, and the specific site on the protein that the immune system recognizes. Epitopes are also where IgE antibodies bind to the protein.
Back in 2008, Sampson and colleagues published a study showing that when there is IgE antibody binding to a wide variety of epitopes on the peanut proteins Ara h 1, 2 and 3, allergic children were more likely to have severe reactions.
In 2021, Sampson and colleagues published follow-up research that found two epitopes on Ara h 2 to be particularly important. When IgE antibodies bound to those two epitopes, their testing predicted peanut allergy with over 90 percent accuracy. (Skin testing has a high rate of false positives, about 50 percent).
Who Reacts to Peanut Traces?
The researchers wondered if epitope profiling could reveal even more. Namely, who among the allergic would react to trace amounts of peanut and who had a milder allergy.
In the latest study, Sampson and his team used blood samples and data on oral food challenges in over 400 children and adults. The data is from five previous, placebo-controlled peanut allergy studies.
They then pinpointed key binding sites on the Ara h 2 and Ara h 3 proteins that predicted how much peanut a patient could eat before beginning to react. From there, they grouped study subjects into three levels of reactivity.
- The “low” group reacted to the lowest amount of peanut. That group was 92 percent likely to tolerate 4 milligrams of peanut before reacting, but only 77 percent could tolerate 14 mg, 53 percent could tolerate 44 mg, and 29 percent could tolerate 144 mg peanut (about half a peanut.) Only 10 percent could tolerate 444 milligrams of peanut (about 1½ peanuts).
- The “high” group could tolerate considerably more peanut before reacting. That group was 98 percent likely to tolerate 4 mg, 95 percent likely to tolerate 14 mg, 94 percent likely to tolerate 44 mg, and 88 percent likely to tolerate 144 mg. Nearly three in four (73 percent) could tolerate 444 mg.
- The “moderate” group fell in between. For example, that group had a 67 percent chance of tolerating 144 mg before starting to react, while 36 percent could eat 444 mg of peanut.
On average, those in the high group were four times more likely to tolerate a specific dose of peanut compared to the low group. (The test does not determine how severe any given reaction will be.)
“Some people will react to the tiniest amount,” says Sampson. “For those in the higher groups, we are not saying ‘go out and be reckless.’ But I have patients who are afraid to go to restaurants or parties, because they are so fearful of a small amount of contamination. If they are the high group, I could reassure them that, even if there is a small amount of peanut present in the food, you will be fine.”
Helping Families Make Decisions
Peanut allergies affect about 2 percent of the U.S. population. About 80 percent of children with a peanut allergy will not outgrow it.
Although the epitope threshold test from Allergenis is new, Sampson and other allergists say the results are already impacting their advice to patients. And it’s affecting the decisions families make about managing or treating the peanut allergy.
For example, if a child is in the most reactive group, some families may decide to double down on efforts to be vigilant with avoiding peanuts. Other families may conclude that it’s a good reason to pursue oral immunotherapy, which can increase tolerance.
Sampson notes that some families think OIT is too much of a burden to undertake. “Only about 10 percent want to go ahead and do it,” he says. But with a patient in that low group, “I would be telling them they are at a pretty high risk [for anaphylaxis]. OIT is burdensome and there are adverse reactions associated with it, but you should still consider it.”
Sampson and his team are continuing to study epitopes for use in diagnosing milk, egg and wheat allergies. Also under study: whether epitope binding can predict who will tolerate baked milk.
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