Allergen Profile, Hazelnut, IgE With Component Reflexes*

The measurement of specific immunoglobulin E (IgE) to individual components of an allergen, either purified native or recombinant, is referred to as component resolved diagnosis (CRD).^1-6 This approach represents an improvement over traditional measurement of IgE to allergen extracts that contain a mixture of proteins. The pattern of specific IgE reactivity to component allergens can predict which patients are at higher risk for systematic allergic reactions versus those who are sensitized but clinically tolerant. CRD can also be used to predict which patients are at risk for more severe reactions and which patients are likely to have milder symptoms.

Allergies to plant-derived foods can occur as the result of sensitization to relatively stable proteins, such as the seed storage or lipid transfer proteins. Sensitization to this type of protein can be associated with more severe, systemic reactions and a higher risk for anaphylaxis.^1,7 Alternatively, allergies to plant-derived foods may occur in pollen-sensitized individuals due to pollen allergens that cross-react with food allergens.¹ Examples of pollen-associated allergens are the profilins or PR10 proteins that are homologues of the major white birch pollen antigen Bet v 1.

Allergy to this family of proteins is associated with symptoms that are generally limited to the oropharyngeal area (commonly referred to as the oral allergy syndrome of pollen food allergy syndrome).

Component resolved diagnostics can help to^1-6:

• Distinguish between allergy due to cross-reactivity and primary allergy.

• Improve the risk assessment using allergen components.

• Improve management of allergic patients.

Hazelnut

• Hazelnut is among the top five most serious causes of food allergic reactions.^1,8,9

• The prevalence of hazelnut allergy in children is estimated to 0.2%, while up to 4.5 % of adults in regions with heavy exposure to pollen of birch or related tree species are reported to have hazelnut allergy.¹⁰

• Primary sensitization to hazelnut is more common in children than in adults, and children more often develop severe and systemic reactions to hazelnut.^1,11,12

• Hazelnut may be a hidden allergen in pastries and cookies.¹³

Hazelnut Components

Cor a 9

Cor a 14

• Cor a 9 and Cor a 14 are hazelnut storage proteins, and sensitization to these can appear early in life.^14-16

• These are storage proteins that serve as the energy source for the seed during growth of a new plant.

• Sensitization to storage proteins Cor a 9 and/or Cor a 14 has been associated with systemic reactions in hazelnut allergic patients.^11,14-22

• Hazelnut allergic patients sensitized to storage proteins should also be investigated for allergy to peanuts and other tree nuts, eg, walnuts and Brazil nuts, as cross-reactivity may occur.^13,18,23

^{Cor a 1}

• Cor a 1 has a high degree of homology to the major birch allergen Bet v 1. These two proteins display extensive cross-reactivity.^24,25

• Birch-sensitized individuals are frequently co-sensitized to peanut Cor a 1.

• Sensitization to this birch pollen cross-reactive allergen varies depending on local exposure to birch pollen and is mainly observed in birch-endemic regions.²⁵

• A diagnosis of hazelnut allergy is complicated by the presence of Cor a 1, a heat-labile protein that cross-reacts with the birch pollen allergen, Bet v 1.^19,25

• Sensitization to Cor a 1 is often associated with oropharyngeal symptoms in a condition that is referred to as the pollen-food syndrome.^8,9,11

• Mono-sensitization to Cor a 1 is typically associated with local reactions, although systemic reactions to raw hazelnuts may in some cases occur, especially in adults.¹¹

• Patients mono-sensitized to Cor a 1 often tolerate roasted or heated hazelnuts.²⁶

• In patients who do not have a history of objective symptoms on ingestion of hazelnut and whose elevated hazelnut sIgE levels may be attributed to elevated birch sIgE levels, component testing could give a better indication of patients who are clinically reactive to hazelnut.^19,22,27

^{Cor a 8}

• Cor a 8 is a lipid transfer protein (LTP) that is structurally similar to lipid transfer proteins found in several fruits.^28-30

• Hazelnut allergy caused by Cor a 8 sensitization is often associated with symptoms to other LTP-containing food such as peach, lettuce, peanut, walnut, and cherry.³¹

• Sensitization to Cor a 8 is thought to be frequently caused by sensitization to a similar LTP from peach.^28-30

• The presence of IgE antibodies to Cor a 8 can be associated with either local oral symptoms or systemic reactions.^7,11,26,28

• In reports from the Mediterranean area, systemic reactions to hazelnut are often mediated by IgE to Cor a 8.^13,22

• While studies of Mediterranean populations have found Cor a 8 to be linked to more severe symptoms, sensitization to this component has not been found to be of great importance in predicting clinical reactivity to hazelnut in studies from other regions.^12,31,32

General Comments

• Hazelnut allergy in a birch-endemic region exhibits age-related sensitization profiles with distinct clinical outcomes that can be identified using CRD.^1,11,14,33

• The majority of hazelnut allergic preschool and school children (prior sensitization to birch pollen) show systemic reactions on consumption of processed hazelnut, mostly being sensitized to the Cor a 9 and Cor a 14.^11,19,20,24

• In contrast, adults often suffer from oropharyngeal symptoms (the pollen-food syndrome) ostensibly as a result of cross-reactivity between Cor a 1 from hazelnut and Bet v 1 from birch pollen.^{1,11,12,19,24}

• Adults from regions where birch is not endemic generally frequently demonstrate a systematic allergy symptoms that seem to originate from a cross-reactivity between the LTP Cor a 8 from hazelnut and its counterpart from peach.^{1,12,19,22,24}

• Hazelnut allergic patients sensitized to Cor a 8, Cor a 9, and/or Cor a 14 should avoid raw as well as roasted/heated hazelnuts.³²