Diagnosing Food Allergy

The gold standard for diagnosing food allergy is an oral food challenge. In this procedure, a food is eaten slowly, in gradually increasing amounts, under medical supervision to accurately diagnose or rule out a true food allergy. However, physicians use oral food challenges cautiously because the procedure is time-consuming, requires highly trained personnel, and can cause an acute allergic reaction.

The most frequently used food allergy diagnostics are the allergy skin-prick test and the allergy blood test. In a skin-prick test, a lancet is used to prick the skin under a drop of allergen extract. If a person is allergic to the allergen, a raised red bump will appear at the site of the prick after about 15 minutes. An allergy blood test measures the level of a type of antibody called immunoglobulin E (IgE) that is specific to a particular food or a protein within the food. People who have a food allergy make more IgE than normal to that food or protein.

Unfortunately, the results of these tests may indicate that a person has a food allergy when they really don’t—a result known as a false positive. A physician may consequently place an individual on an unnecessarily restrictive food-elimination diet, which can lead to poor weight gain, malnutrition, and reduced quality of life. This is an issue especially for people with atopic dermatitis, who are likely to have high total IgE levels and positive skin-prick or blood tests for foods but may not necessarily have a food allergy.

To avoid such misdiagnoses and poor health outcomes, an NIAID clinical trial begun in 2019 aims to identify threshold IgE levels to peanut and milk or a component of these foods that predict whether a person has a food allergy. This would clarify when it makes sense to do an oral food challenge to make a definitive diagnosis. The participants in the NIAID trial are people with atopic dermatitis who have a high total IgE level and may have an allergy to milk, peanut, or both. The study is expected to continue through 2027.

A Next-Generation Allergy Blood Test

To improve upon the allergy blood test, Pamela A. Guerrerio, M.D., Ph.D., chief of the NIAID Laboratory of Allergic Diseases, co-created a diagnostic tool called AllerScan with collaborators at Johns Hopkins School of Medicine in Baltimore. By analyzing a much smaller blood sample than required for typical allergy tests, this technology may help distinguish food allergy from food sensitization and non-allergy and may be useful for monitoring a person’s response to allergy treatment. Food sensitization means a person has a positive IgE test to a food but can still tolerate that food in their diet.

AllerScan is unique because it zooms in on allergenic epitopes, or the specific points where anti-allergen IgE antibodies bind to the proteins of allergens. This is important because several epitopes within a protein can be responsible for IgE reactivity. AllerScan can tease out IgE antibodies from blood that react to any protein epitope identified to date as a food or environmental allergen.

To test the new technology, Dr. Guerrerio and colleagues used AllerScan to examine the blood of people who had either wheat allergy, wheat sensitivity, or no allergy. Common diagnostic tools frequently yield false positives for wheat allergy, most likely because of cross-reactivity with grass pollen allergens.

AllerScan detected that people with wheat allergy tended to have an IgE response to an epitope in a wheat protein called alpha purothionin. By contrast, people with wheat sensitivity or no wheat allergy had a strong response to the alpha purothionin epitope by a different type of antibody called immunoglobulin G (IgG), which is known to block the effects of IgE. Wheat-allergic individuals who subsequently underwent oral immunotherapy to treat their allergy had a reduction in the number of wheat protein epitopes to which IgE antibodies reacted and an increase in the number of wheat protein epitopes to which IgG antibodies reacted. These findings were reported in the journal Nature Communications in 2021.

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