Component testing for food allergy
Introduction
In 2021, the percentage of children in the United States with food allergy was approximately 6% as reported by the Centers for Disease Control and Prevention.1 Allergies develop when a person has produced IgE antibody (ie, is sensitized) to specific food component proteins on initial exposure and then has a reaction after being re-exposed to the same food. A reaction can also occur when these IgE antibodies cross-react with similar component proteins in a different food. However, some children may be only sensitized to an antigen without having a true allergy.
A true allergic reaction to a food is also called an IgE-mediated (ie, type I) hypersensitivity reaction. Symptoms occur within seconds of exposure to a food or food group and can be severe; in rare cases, the reaction is fatal. Importantly, some individuals who are IgE-sensitized to a food will not develop symptoms if the food is ingested again.2 Therefore, patients with positive IgE test results for a specific food fall into 2 categories: (1) IgE-sensitized and allergic and (2) IgE-sensitized but not allergic. While whole-food IgE testing may not distinguish between these 2 groups of patients, food component IgE testing detects IgE to different proteins within a food and can help better differentiate whether or not an IgE-sensitized patient has a true allergy.3,4
Diagnostic testing
For patients with suspected food allergies (eg, peanut, tree nuts, milk, eggs), serum IgE tests or skin prick tests (SPTs) are recommended.5 Testing should focus on foods suspected of provoking a reaction or which have been recently ingested and should be used in conjunction with the patient’s clinical history (eg, recent ingestion, clinical reaction).6
Serum IgE tests and SPTs are standard diagnostic tests, but these methods do not reliably distinguish IgE sensitization from true allergy. In peanuts, for example, a substantial overlap is observed in the distribution of peanut-specific IgE levels of sensitized patients with and without a true peanut allergy.7 The oral food challenge (OFC), considered the gold standard in diagnostic testing for food allergies, can help diagnose food allergies if a clinical history or test results are insufficient to establish a diagnosis; however, OFC is expensive and puts the patient at risk for an anaphylactic reaction.8
Component testing can distinguish patients with a true food allergy from those who are only IgE-sensitized, without the risk of anaphylactic shock from an OFC.4,6 Depending on the specific component targets(s) of IgE reactivity (Table 1),9-15 a patient may be at low, variable, or high risk of a true allergy to the food of concern.
Table 1. Whole Food and Components
Whole food |
Component proteins |
Meaning of positive IgE reaction (component IgE profiles)9-15 |
Peanut |
Ara h 1, 2, 3, 6 |
Ara h 2 is nearly always associated with clinical allergy; presence of any of these 4 components indicates high risk of systemic reaction including anaphylaxis |
Ara h 9 |
Variable risk of strong allergic reaction (often accompanied by sensitization to other peanut proteins) |
|
Ara h 8 |
Low risk of systemic reactions Associated with local reactions or no reaction at all |
|
Tree nuts Hazelnut |
Cor a 9,14 |
Presence of any of these 5 components indicates high risk of systemic reactions including anaphylaxis |
Hazelnut Cor a 8 |
Associated with mild local reactions, as well as systemic reactions |
|
Hazelnut Cor a 1 |
Low risk of systemic reactions |
|
Milk |
Casein |
High risk of reaction to all forms of cow’s milk |
α-lactalbumin and β-lactoglobulin |
High risk of reaction to fresh cow’s milk |
|
Egg |
Ovomucoid |
High risk of reaction to all forms of egg |
Ovalbumin |
High risk of reaction to fresh eggs |
Structural similarities of proteins within food families may cause IgE cross-reactivity. Consequently, component testing can help determine the likelihood that a patient who is allergic to one food will also react to other potentially cross-reactive foods.
Component testing examples
Tree nuts and peanuts
Different nut component proteins may elicit systemic reactions, local reactions, or no reaction at all, depending on their resistance to heat and enzymatic digestion.16,17 In peanuts, for example, storage proteins (eg, Ara h 1, Ara h 2, Ara h 3, Ara h 6) are resistant to digestion and can trigger systemic reactions (most commonly Ara h 2), whereas PR-10 (eg, Ara h 8) is heat- and digestion-labile. IgE reactivity to PR-10 alone usually results in no or local reactions (Table 2).18,19 Therefore, IgE reactivity to Ara h 1-3, and/or 6 supports a diagnosis of a true peanut allergy and may require dietary restrictions and anaphylaxis precautions during meals, while sensitization to Ara h 8 alone would suggest a low risk for a true peanut allergy, and continued peanut consumption would likely be appropriate.20
Table 2. Component Protein Families in Tree Nuts and Peanuts
Protein family |
Component protein |
Source |
Stability |
Cross-reactivity to IgE18,19 |
Storage protein |
Ana o 3 |
Brazil nut, cashew, hazelnut, peanut, walnut |
Stable to both heat and digestion; therefore, can cause systemic reactions |
Relatively species-specific |
Lipid transfer protein |
Ara h 9 |
Hazelnut, peanut |
Stable to heat and digestion; therefore, can cause systemic reactions |
Varies |
PR-10 protein |
Ara h 8 |
Hazelnut, peanut |
Heat and digestion labile. Primarily causes local clinical reactions |
Varies |
Profilin |
Ara h 5 |
Brazil nut, cashew, hazelnut, peanut, walnut |
Heat and digestion labile. Primarily causes no or local clinical reactions |
Extensive |
The structural similarities of proteins throughout the plant kingdom also affect their potential for IgE cross-reactivity (Table 2).21 For example, walnuts, pecans, and hazelnuts form a group of strongly cross-reactive tree nuts22; thus, an individual with IgE to allergenic components in walnuts can also be allergic to pecans and hazelnuts. IgE cross-reactivity also explains why individuals can have IgE to certain foods, such as peanuts and tree nuts, but not exhibit true allergy. Exposure to profilin or bromelain and its cross-reactive carbohydrate determinant (CCD) MUXF3—found throughout the plant kingdom—can cause sensitization, but these allergens are not associated with true allergy.23
By identifying specific protein components that are common among certain nut or plant species, component testing may help guide dietary restrictions to include or exclude foods based on the potential for allergic reactions due to IgE cross-reactivity.
Milk and eggs
In their native conformations, milk and egg proteins may cause mild to severe allergic reactions in IgE-sensitized patients (Table 1).21,24 Patients with IgE reactivity to milk and egg proteins that are resistant to heat or digestion (eg, casein, ovomucoid) are most likely to have allergic reactions to these foods. However, many patients who are IgE-sensitized primarily to heat-labile milk and/or egg component proteins (eg, α-lactalbumin, β-lactoglobulin, ovalbumin) can tolerate eggs and/or milk in baked goods even though they react to these foods when uncooked or undiluted by other ingredients.25
Test availability
Quest Diagnostics offers whole-food IgE testing with reflex to components if whole-food IgE testing is positive for certain foods (Appendix).
References
Appendix
Food Allergy Panels and Testsa,b
Test name |
Test code |
Brazil Nut (f18) IgE with Reflex to Component |
|
Cashew Nut (f202) IgE With Reflex to Component |
|
CCD (o214) IgE |
|
CCD and Profilin IgE Cross-Reactivity Panel |
|
Childhood Allergy (Food and Environmental) Profile With Reflexes Includes Alternaria alternata (m6, 2706), cat dander (e1, 10564) with reflex to cat components, Cladosporium herbarum (m2, 2702), cockroach (i6, 2736), codfish (f3, 2803), cow's milk (f2, 37900) with reflex to milk components, Dermatophagoides farinae (d2, 2722), Dermatophagoides pteronyssinus (d1, 2721), dog dander (e5, 10571) with reflex to dog components, egg white (f1, 37906) with reflex to egg components, mouse urine proteins (e72, 2658), peanut (f13, 91747) with reflex to peanut components, shrimp (f24, 2824), soybean (f14, 2814), walnut (f256, 3489), wheat (f4, 2804), and total IgE. |
|
Childhood and Tree Nut Allergy Panel With Reflex to Components Includes Alternaria alternata (m6, 2706), almond (f20, 2820), Brazil nut (f18, 94464) with reflex to Brazil nut components, cashew nut (f202, 94465) with reflex to cashew nut components, cat dander (e1, 10564) with reflex to cat components, Cladosporium herbarum (m2, 2702), cockroach (i6, 2736), codfish (f3, 2803), cow's milk (f2, 37900) with reflex to milk components, Dermatophagoides farinae (d2, 2722), Dermatophagoides pteronyssinus (d1, 2721), dog dander (e5, 10571) with reflex to dog components, egg white (f1, 37906) with reflex to egg components, hazelnut (f17, 94468) with reflex to hazelnut components, macadamia nut (rf345, 38475), mouse urine proteins (e72, 2658), peanut (f13, 91747) with reflex to peanut components, shrimp (f24, 2824), soybean (f14, 2814), walnut (f256, 94467) with reflex to walnut components, wheat (f4, 2804), and total IgE. |
|
Cow's Milk (f2) IgE With Reflex to Milk Component Panel |
|
Egg Component Panel Includes ovalbumin (f232) IgE, ovomucoid (f233) IgE |
|
Egg White (f1) IgE With Reflex to Egg Component Panel |
|
Food Allergy Profile With Reflexes Includes almond (f20, 2820), cashew nut (f202, 2608), codfish (F3, 2803), cow's milk (f2, 37900) with reflex to milk components, egg white (f1, 37906) with reflex to egg components, hazelnut (f17, 2817), peanut (f13, 91747) with reflex to peanut components, salmon (f41, 2841), scallop (f338, 273), sesame seed (f10, 2810), shrimp (f24, 2824), soybean (f14, 2814), tuna (f40, 2840), walnut (f256, 2804), and wheat (f4, 2804) IgE. |
|
Food and Tree Nut Allergy Panel With Reflex to Components Includes almond (f20, 2820), Brazil nut (f18, 94464) with reflex to Brazil nut components, cashew nut (f202, 94465), with reflex to cashew nut components, codfish (f3, 2803), cow's milk (f2, 37900) with reflex to milk components, egg white (f1, 37906) with reflex to egg components, hazelnut (f17, 94468) with reflex to hazelnut components, macadamia nut (rf345, 38475), peanut (f13, 91747) with reflex to peanut components, salmon (f41, 2841), scallop (f338, 273), sesame seed (f10, 2810), shrimp (f24, 2824), soybean (f14, 2814), tuna (f40, 2840), walnut (f256, 94467) with reflex to walnut components, and wheat (f4, 2804) IgE. |
|
Hazelnut (f17) IgE With Reflex to Component |
|
Hazelnut Component Panel Includes Cor a1 (f428), Cor a8 (f425), Cor a9 (f440), Cor a14 (f439) |
|
Milk Component Panel Includes alpha-lactalbumin (f76) IgE, beta-lactoglobulin (f77) IgE, casein (f78) IgE |
|
Peanut Component Panel |
|
Peanut, Total With Reflex to Peanut Component |
|
Profilin (t216) IgE |
|
Tree Nut Allergy Panel With Reflex to Components Includes almond (f20, 2820), Brazil nut (f18, 94464) with reflex to Brazil nut components, cashew nut (f202, 94465) with reflex to cashew nut components, hazelnut (f17, 94468) with reflex to hazelnut components, macadamia nut (rf345, 38475), peanut (f13, 91747) with reflex to peanut components, pecan (f201, 2864), pistachio (f203, 2726), and walnut (f256, 94467) IgE with reflex to walnut components |
|
Walnut Component Panel Includes rJug r1 (f441), rJug r3 (f442) |
|
Walnut (f256) IgE With Reflex to Component |
| a | Reflex tests are performed at an additional charge and are associated with an additional CPT® code(s). CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed. |
| b | Component panels or tests can be ordered separately. |
Content reviewed 9/2025
This allergen-specific IgE antibody test quantifies an individual's IgE response to German cockroach, an insect commonly found in urban environments with temperate climates. Exposure to cockroach allergens is associated with asthma, especially among children and young adults [1]. This test is an in vitro quantitative assay that is intended to be used in conjunction with other clinical information to aid in the diagnosis of allergic diseases [2].
While allergen-specific serum IgE testing is considered comparable to skin testing in many instances, both the American Academy of Allergy, Asthma, and Immunology and the American College of Allergy, Asthma, and Immunology recognize that allergen-specific serum IgE testing may be preferred in some clinical situations. These include (1) the presence of widespread skin disease, (2) the recent use of antihistamines or other medications that can affect the results of allergy skin tests, (3) uncooperative patients, and (4) medical history suggesting that allergen skin testing would pose a significant risk for a serious allergic reaction [2].
A definitive clinical diagnosis of allergy should not be based on the results of any single diagnostic method but should be made by a trained healthcare provider after all clinical and laboratory findings have been evaluated.
More specific information about this allergen can be found on the following web page: https://www.thermofisher.com/diagnostic-education/hcp/us/en/resource-center/allergen-encyclopedia/whole-allergens.html?key=i6
References
1. Pomes A, et al. Curr Allergy Asthma Rep. 2017;17(4):25.
2. Bernstein IL, et al. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3)S1-S148.
This allergen-specific IgE antibody test quantifies an individual's IgE response to Dermatophagoides pteronyssinus, a species of house dust mites that can cause atopic reactivity and allergic disease affecting the eyes, airways, skin, and occasionally the circulation [1]. This test is an in vitro quantitative assay that is intended to be used in conjunction with other clinical information to aid in the diagnosis of allergic diseases [2].
While allergen-specific serum IgE testing is considered comparable to skin testing in many instances, both the American Academy of Allergy, Asthma, and Immunology and the American College of Allergy, Asthma, and Immunology recognize that allergen-specific serum IgE testing may be preferred in some clinical situations. These include (1) the presence of widespread skin disease, (2) the recent use of antihistamines or other medications that can affect the results of allergy skin tests, (3) uncooperative patients, and (4) medical history suggesting that allergen skin testing would pose a significant risk for a serious allergic reaction [2].
A definitive clinical diagnosis of allergy should not be based on the results of any single diagnostic method but should be made by a trained healthcare provider after all clinical and laboratory findings have been evaluated.
More specific information about this allergen can be found on the following web page: https://www.thermofisher.com/diagnostic-education/hcp/us/en/resource-center/allergen-encyclopedia/whole-allergens.html?key=d1
References
1. Miller JD. Clin Rev Allergy Immunol. 2019;57(3):312-329.
2. Bernstein IL, et al. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3)S1-S148.
Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.
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