Allergy & Immunology

Food Allergies

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The Role of Biomarkers in the Management of Food Allergies

expert roundtables by Terri F. Brown-Whitehorn, MD; Ruchi Gupta, MD, MPH; Edwin Kim, MD, MS
Overview

Although oral food challenges (OFCs) are considered the gold standard for the diagnosis of food allergies, their use is not without risk. Therefore, biomarkers are being investigated to assist with food allergy identification and follow-up. Our expert panel discusses the role of currently available biomarkers and those in development for food allergy management.

What biomarkers are currently clinically used in the diagnosis and management of food allergies, and do they have any prognostic significance? What is the potential clinical role of biomarkers in development?
“It would be ideal if we could diagnose more people without the use of OFCs and, instead, just reserve them for those truly equivocal cases.”
— Edwin Kim, MD, MS

Biomarkers are definitely a very hot topic right now, particularly with some of the newer therapies such as omalizumab becoming US Food and Drug Administration (FDA) approved and others getting closer to coming to the market. Skin and IgE testing have been available to us for many years and, in the hands of allergists, can be quite accurate. Unfortunately, these tests inherently have high false-positive rates. Specifically with IgE testing, it is very easy to order large panels of these tests, but without proper interpretation, they run the risk of overdiagnosing allergies, which can have multiple effects. One is unnecessary allergen avoidance, and another is people getting unnecessary therapy.

 

Because of the drawbacks of our current biomarkers, OFCs are not going away. I think that they are the definitive test for food allergies, but it would be hugely beneficial if we could narrow down the number of patients who need an OFC because access to OFCs is not broad. It would be ideal if we could diagnose more people without the use of OFCs and, instead, just reserve them for those truly equivocal cases.

 

For patients who are in treatment, I think that there is a question of how we will know if someone’s food allergies are actually getting better. We try to use the same biomarkers, but all we can speak to is trends. So, if the skin test reaction is smaller and IgE titers are reduced, that may suggest that a patient is improving. However, these do not have accuracy to the point where we can translate the results into an amount of protection from allergen exposure, so that is a huge gap.

 

The basophil activation test (BAT) has been around for quite a while and is probably the test that is discussed the most. In the hands of some experts, it is really good; however, it is a very unwieldy test because of required blood volumes and timing, and not every center can do it. We are trying to determine if we can take the expertise of these centers that can administer the BAT and get it out to more people.

“Since we know that some children may outgrow certain food allergies, biomarkers can also be important for following a child's food allergy over time.”
— Terri F. Brown-Whitehorn, MD

OFCs remain the gold standard for the diagnosis of food allergies and for assessing whether one has outgrown their food allergy. There are 3 potential outcomes: the patient tolerates the food and has outgrown their allergy, the patient is unable to complete the OFC and the challenge is indeterminant, or the patient has a reaction at a certain amount and is treated with medications. The problem with the latter outcome is that the reaction can either be mild and unpleasant or uncomfortable, or it can be quite severe. This is one of the important reasons that many researchers and clinicians are looking for other means of diagnosing and following food allergies.

 

Using biomarkers shows promise, but they are not available for all foods, and they do not always correlate with threshold doses. Since we know that some children may outgrow certain food allergies, biomarkers can also be important for following a child’s food allergy over time.

 

I also want to reiterate that we do not recommend large food allergy panels, especially in a child who has not yet been exposed to the food or in a child in whom the food is already a part of their diet. The ideal way to use this testing is to look at the specific food(s) in question. There is a high false-positive rate, leading to the potential of unnecessary dietary restrictions affecting both the patient’s overall nutrition and food costs. As with all allergy testing, especially for food, working with clinicians who are used to ordering and reviewing these values is key.

“Having more accurate diagnostics is critical to predict food allergies, especially for underserved children and those living in rural areas who may not be able to access allergists. Food allergies may be overdiagnosed in these populations because doctors are not able to test or they are using IgE alone, which can have a high false-positive rate.”
— Ruchi Gupta, MD, MPH

We are moving away from allergy panels, and this is really important. Allergen component testing is helpful for certain foods for which we have really good data, such as peanuts. Epitope mapping is also available, but I do not think that it is being used as much, as is the BAT, which people are trying to make easier to administer and interpret. Hopefully, more of these more accurate tests will be used as time goes on. I think that the field is moving really fast, although, right now, a thorough history and an OFC are the gold standards for diagnosis.

 

Having more accurate diagnostics is critical to predict food allergies, especially for underserved children and those living in rural areas who may not be able to access allergists. Food allergies may be overdiagnosed in these populations because doctors are not able to test or they are using IgE alone, which can have a high false-positive rate.

 

Sometimes, food epitope mapping predicts that someone will not be allergic to something, but the person still ends up failing an OFC. However, if a patient knows that it takes half a peanut for them to react, this information can give them confidence in terms of their threshold, which I think is very important. It means that the patient can eat foods with precautionary allergen statements and some foods that may have a little cross-contact, because they know that their threshold is higher and that they will not react until they get to a certain level. Understanding threshold and severity is important to people, and, if we had testing to tell what category someone is in, it would really help families.

References

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Esty B, Maciag MC, Bartnikas LM, et al. Predicting outcomes of baked egg and baked milk oral food challenges by using a ratio of food-specific IgE to total IgE. J Allergy Clin Immunol Pract. 2021;9(4):1750-1752.e1. doi:10.1016/j.jaip.2020.11.004

 

Foong RX, Santos AF. Biomarkers of diagnosis and resolution of food allergy. Pediatr Allergy Immunol. 2021;32(2):223-233. doi:10.1111/pai.13389

 

Kim H, Jeong K, Park M, et al. Predicting the outcome of pediatric oral food challenges for determining tolerance development. Allergy Asthma Immunol Res. 2024;16(2):179-190. doi:10.4168/aair.2024.16.2.179

 

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Meyer R. Nutritional disorders resulting from food allergy in children. Pediatr Allergy Immunol. 2018;29(7):689-704. doi:10.1111/pai.12960

 

Parrish CP. A review of food allergy panels and their consequences. Ann Allergy Asthma Immunol. 2023;131(4):421-426. doi:10.1016/j.anai.2023.04.011

 

Taylor-Black S, Wang J. The prevalence and characteristics of food allergy in urban minority children. Ann Allergy Asthma Immunol. 2012;109(6):431-437. doi:10.1016/j.anai.2012.09.012

 

Xie Q, Xue W. IgE-mediated food allergy: current diagnostic modalities and novel biomarkers with robust potential. Crit Rev Food Sci Nutr. 2023;63(29):10148-10172. doi:10.1080/10408398.2022.2075312

 

Terri F. Brown-Whitehorn, MD

Attending Physician, Division of Allergy and Immunology
Children's Hospital of Philadelphia
Professor of Clinical Pediatrics
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

Ruchi Gupta, MD, MPH

    Professor of Pediatrics and Medicine
    Director, Center for Food Allergy & Asthma Research
    Northwestern University Feinberg School of Medicine
    Clinical Attending, Ann & Robert H. Lurie Children’s Hospital of Chicago
    Chicago, IL


Edwin Kim, MD, MS

    Associate Professor of Pediatrics and Medicine
    Chief, Division of Pediatric Allergy and Immunology
    Director, UNC Food Allergy Initiative
    Director, UNC Allergy and Immunology Fellowship Program
    University of North Carolina School of Medicine
    Chapel Hill, NC
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