Peanut allergy affects about 2% to 4% of children in the U.S., and often, it does not happen in isolation: Approximately 20% of children with peanut allergy also react to tree nuts, such as cashews and walnuts.
Researchers still don’t fully understand why peanut-allergic children may or may not react to certain tree nuts, or why they react to some tree nuts and not others, since many nuts contain similar proteins. But many children with peanut allergies avoid eating tree nuts altogether when they might not actually need to do so.
Testing for nut allergies also is not always straightforward. The current diagnostic tests for peanut and tree nut allergies often give ambiguous or inconclusive results. In those cases, the most accurate way to find out if someone has a nut allergy is to perform an oral food challenge (OFC) where they ingest increasing doses of the nut in question until it does or does not trigger an allergic reaction.
A team of researchers with the University of Colorado Anschutz Department of Medicine has received an R01 grant from the National Institute of Allergy and Infectious Diseases (NIAID), an institute within the National Institutes of Health (NIH), to study the allergens in peanuts and common allergenic tree nuts. Their ultimate goal? Designing safer tests that can more accurately identify nut allergies without the need for an OFC.
“OFCs are done all the time. But they are expensive, they are time-consuming, and they are potentially dangerous. So, it would be nice to have good tests that would help guide us better,” says Stephen Dreskin, MD, PhD, a specialist in allergy and immunology and adjoint professor of medicine in the Division of Pulmonary, Allergy, and Critical Care Medicine.
Peanuts and tree nuts are often grouped together, but they come from different plant families. Peanuts, which are ground nuts, are legumes, and they are phylogenetically different from tree nuts, such as cashews and walnuts.
However, what both peanuts and tree nuts have in common is that they are all seeds that contain similar proteins to help them sprout and grow into new plants. Some of these proteins can trigger allergic reactions, so understanding the similarities among these allergenic proteins could help researchers improve allergy testing.
Dreskin says most allergens are proteins because they are stable substances that the body can easily recognize and respond to. The allergic response is similar to the way the body defends against parasites. In the case of food allergies, the immune system mistakenly interprets food proteins as dangerous parasitic invaders and mounts a full-scale defense, resulting in allergic reactions.
Peanut allergy became much more widespread in the 1970s, 80s, and 90s, a stretch of time when many parents preemptively stopped feeding their children peanuts for fear that they might be allergic. Recent research suggests that expecting and new mothers could lower the risk of peanut allergy in their children by eating peanut-containing snacks during pregnancy and breast feeding.
However, not all children are good candidates for early introduction of peanuts, and parents should consult with a pediatrician. And although this approach shows promise for preventing peanut allergy, research regarding the efficacy and safety of early introduction of other allergenic foods is still underway.
Standard diagnostic tests for peanut and tree nut allergies include skin tests and blood tests that measure a type of allergy-specific antibody called IgE. When someone with a peanut allergy is exposed to peanuts, for example, their body creates IgE antibodies that bind to the specific allergenic proteins in peanuts and trigger an allergic reaction. The immune system marshals its resources to fight off what it thinks is a foreign invader.
Generally, a higher level of IgE antibodies suggests a higher level of sensitivity, or allergy, to peanuts. But roughly 75% of children tested show higher-than-average levels of IgE antibodies while falling short of the established lab cutoff for a clear diagnosis of peanut allergy. That ambiguity is why so many doctors resort to oral food challenges, or OFCs, to determine for sure whether there is an allergy.
Because IgE levels do not always correspond perfectly to the strength of the allergic response someone might have, it is difficult to tell with current testing which patients could tolerate an OFC, or which ones might respond to oral immunotherapy, which gradually exposes patients to tiny doses of allergens to desensitize the body to them.
To improve peanut and tree nut allergy testing, Dreskin and his fellow researchers have zeroed in on measuring IgE binding to the protein Ara h 2, which is thought to be the most powerful allergen in peanuts. Their initial work examined small peptides — smaller, protein-like chains of amino acids — that are part of Ara h 2.
But one challenge they’ve encountered is that Ara h 2 is a 3D protein, whereas the peptides being studied are 2D. So, the Dreskin lab has focused on discovering “mimotopes,” or peptides that “mimic” the 3D parts of Ara h 2 that IgE might bind to. Their early results suggest these mimotopes may significantly enhance the accuracy of allergy tests.
The hope is that these new and improved tests could distinguish real peanut allergy from sensitivity, determine how sensitive someone will be to an OFC, and predict whether they will benefit from oral immunotherapy. Eventually, Dreskin’s team plans to expand outward and also study the allergens in cashews and walnuts, but for now, they are primarily focusing on peanuts.
Dreskin says he is encouraged by how the research is progressing and he is hopeful this work will move the needle toward meaningfully improving care for patients with peanut allergy.
“It's very exciting, it's a lot of fun, and we really think this is going to be very useful,” he says.