Updated Oct. 1, 2021 – A blood test called “epitope mapping” accurately predicted peanut allergy 93 percent of the time, a recent study finds.
Researchers say the new test is a significant improvement on existing tests for diagnosing peanut allergy, including skin prick tests and allergen-specific IgE blood tests. Those current tests can be unreliable in determining who will actually experience an allergic reaction to peanuts.
A history of reactions and a skin test will still be important for allergists in diagnosing a peanut allergy, explains senior study author Dr. Hugh Sampson. “But if those were inconclusive or I needed further evidence, I would order this test,” says the director emeritus of the Jaffe Food Allergy Institute at the Icahn School of Medicine at Mount Sinai.
He would do this rather than ordering the current blood test that looks for peanut IgE antibodies (the markers of an allergy) or a peanut component test. With epitope mapping, “this would more accurately tell me whether this person was going to react,” says Sampson.
He says the new test is also one step closer to being able to eliminate the need for the oral food challenge to diagnose a peanut allergy. That test’s the gold standard, but is stressful, since it involves consuming the allergen.
Allergenis, the Pennsylvania-based company that’s commercializing the epitope mapping test for peanut allergy and funding the research, says more applications look promising. Epitope mapping is also being studied to create a test that determines how much peanut a person can consume without reacting. Data on that is expected to be released this summer, Sampson says. If a threshold level can be confirmed, that would be a big development in the field of food allergy.
As well, the epitope mapping test is being studied for other food allergens, including milk and egg.
The Protein Bits That Bind
To develop the peanut diagnostics test, researchers first used machine learning to analyze IgE binding to specific peanut epitopes in blood samples collected from 133 children who had been in the well-known LEAP allergy prevention study.
From the samples, the research team identified sites on peanut protein that, when IgE binds to it, predict allergic reactions. Those binding sites, or epitopes, are sequences of 10 to 15 amino acids, the building block components of proteins.
While everyone who is allergic to peanuts produces IgE antibodies to peanut, it’s more than just IgE levels that determine who will react when they eat peanut, Sampson says. How well the IgE binds to peanut protein, and the sites on the protein where the antibodies bind, can vary from person to person and influence whether someone will experience symptoms.
The study initially looked at 64 possible epitopes, on Ara h 1, 2 and 3, all peanut proteins implicated in allergic reactions. But further analysis showed that high levels of IgE antibodies to just two epitopes on Ara h 2 were associated with a 93 percent chance of also reacting to peanut.
The results needed to be validated, so the team of experts from Mount Sinai, Stanford University and London’s Kings College repeated epitope mapping. To do so, they used blood blood samples from an additional 166 adults and children participating in two other allergy studies, CoFAR2 and POISED. They found similar results.
“We were able to identify which particular epitopes were most often associated with somebody having a clinical reaction to peanut,” Sampson says of the study published online in the journal Allergy. “We came up with a couple of sequences that were better than 90 percent accurate in identifying whether you were going to react.”
The peanut epitope test has met all regulatory requirements and should be available to allergists by late 2021 or early 2022, says Jim Garner, CEO of AllerGenis. How much the test will cost, and whether insurance will cover it, has yet to be determined.
Avoiding False Positives
In some people, a combination of history, a large reaction on a skin-prick test and high levels of peanut IgE in the blood can tell allergists with a high degree of confidence how likely a person is to react to peanut. But existing tests for peanut allergy return a high level of false positives, explains Dr. Brian Schroer, an allergist and immunologist at Akron Children’s Hospital. And that, he says, leads to the overdiagnosis of peanut allergies, with the strict food avoidance lifestyle that follows.
Skin and blood tests have a false positive rate of about 50 percent, meaning that about half of people who have a positive skin or blood test for peanuts won’t actually react to peanuts.
Compare that to the new study’s results on epitope mapping in peanut allergy. The researchers found that positive tests are correct in 92 percent of cases, while negative tests were confirmed in 94 percent of cases. (The testing was confirmed through oral food challenges.)
“This test will significantly cut down those false positives in a way that will be very helpful to make a more informed diagnosis for peanut allergy,” says Schroer, who wasn’t involved in the research. “It’s going to be a very nice test to have.”
The test may eventually replace whole peanut IgE blood tests and peanut-allergen component tests, since the only epitopes that seem to matter are the two on Ara h 2, he says.
Fewer Oral Food Challenges
Epitope mapping may also help avoid the need for some oral food challenges or OFCs, which remain the surest way to determine whether a person is allergic to peanut, Schroer says.
During an OFC, a patient starts off by eating a very low dose of a potential allergen, and the dose is slowly increased over the course of several hours. The test is halted if the patient experiences signs of an allergic reaction.
Many families are anxious about having an allergic child undergo food challenges to confirm whether there’s an allergy, because of the risk that consumption of an allergen may trigger anaphylaxis.
There’s strong interest among allergists and researchers to develop diagnostic tools that are more accurate than the basic food allergy tests, and also reduce the need for food challenges.
“Everyone dealing with food allergies would love to have a simple blood test that can replace the oral food challenge, which remains the gold standard for diagnosing a food allergy but which is very time intensive and carries the risk of anaphylaxis,” Sampson says. “The accuracy of this novel test brings us one step closer to eliminating the need to subject patients to an oral food challenge to diagnose peanut allergy.”
As well, Garner notes that food allergy desensitization trials require OFCs to prove a patient’s allergy for enrollment in a clinical trial, and then on exiting a study. Fear of these challenges can prevent some people from taking part.
Interest Grows in Allergy Testing
After decades with no new tests for food allergy diagnosis, suddenly there is much interest and even a competitive environment for bringing forward new diagnostics.
In addition to epitope mapping, another type of food allergy test being studied is a basophil activation test (BAT). This simulates an oral challenge in a test tube using a blood sample. Using cutting-edge laboratory analysis, this test measures the response of immune cells called basophils when exposed to an allergen. A similar test, mast cell activation test (MAT), uses a patient’s blood plasma and cultured mast cells that are then exposed to an allergen.
In March 2021, the nonprofit FARE (Food Allergy Research and Education) launched the FAITH Challenge, a competition that invites researchers from around the world to submit research ideas for better food allergy testing tools. Proposals will be reviewed by a panel of experts in allergy and immunology, and winning ideas will receive funding from FARE to research and develop the test.
Epitope Testing for Other Foods
Beyond diagnosing peanut allergy, Sampson envisions other uses for epitope mapping. He and his colleagues will soon release data showing that epitope mapping may be able to determine roughly how much peanut someone could consume without reacting.
“We know that not everybody reacts to the same amount of peanut protein,” Sampson says. “Some people are very sensitive, and may react to as little as 1 milligram. But studies suggest that up to 50 percent of people with peanut allergy may tolerate up to 300 milligrams [about ¾ of a peanut kernel] without reacting,” he says. “There is a big gradation to what people react to.”
With the current tests, families and patients with peanut allergies don’t know how great their risk of reacting is, Garner says. “What we want to do with our technology is to provide the answers you would get from an oral food challenge to help guide future treatment decisions.”
Sampson and his team have previously published research using epitope mapping and IgE to predict which toddlers will grow out of a peanut allergy.
They’re also studying epitope mapping to diagnose allergies to other foods, including milk, tree nuts and shrimp. Schroer cautions that it remains to be seen if epitope mapping is as accurate in other foods, which may have more complex protein structures and many more potentially significant epitopes.
“We are all open to new tests being available,” says Schroer. “The questions that will remain with all of these tests is their availability, reliability, cost and practicality.
See the study in the journal Allergy.
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