Allergen Profile, Hazelnut, IgE With Component Reflexes

CPT: 86003
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Test Details

Test Includes

Allergen-specific IgE to whole hazelnut extract. This test reflexes to four molecular components described below.

Use

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 to1-6:

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

• Improve the risk assessment using allergen components.

• Improve management of allergic patients.

Methodology

Thermo Fisher ImmunoCAP® Allergen-specific IgE

Additional Information

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

Link for further information on hazelnut CRD.

Specimen Requirements

Specimen

Serum

Volume

1 mL

Minimum Volume

0.5 mL (Note: This volume does not allow for repeat testing.)

Container

Red-top tube or gel-barrier tube

Storage Instructions

Room temperature

Clinical Information

Footnotes

1. Blanc F, Bernard H, Ah-Leung S, et al. Further studies on the biological activity of hazelnut allergens. Clin Transl Allergy. 2015 Jul 17; 5:26. 26191402
2. Chokshi NY, Sicherer SH. Interpreting IgE sensitization tests in food allergy. Expert Rev Clin Immunol. 2015 Dec; 1-15. 26666347
3. Canonica GW, Ansotegui IJ, Pawankar R, et al. A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics. World Allergy Organ J. 2013 Oct 3; 6(1):17. 24090398
4. Incorvaia C, Rapetti A, Aliani M, et al. Food allergy as defined by component resolved diagnosis. Recent Pat Inflamm Allergy Drug Discov. 2014 Jan; 8(1):59-73. 24483212
5. Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update−2014. J Allergy Clin Immunol. 2014 Nov; 134(5):1016-1025. 25174862
6. Kattan JD, Sicherer SH. Optimizing the diagnosis of food allergy. Immunol Allergy Clin North Am. 2015 Feb; 35(1):61-76. 25459577
7. Pastorello EA, Vieths S, Pravettoni V, et al. Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results. J Allergy Clin Immunol. 2002 Mar; 109(3):563-570. 11898007
8. Flinterman AE, Hoekstra MO, Meijer Y, et al. Clinical reactivity to hazelnut in children: association with sensitization to birch pollen or nuts? J Allergy Clin Immunol. 2006 Nov; 118(5):1186-1189. 17088148
9. Flinterman AE, Akkerdaas JH, Knulst AC, van Ree R, Pasmans SG. Hazelnut allergy: From pollen-associated mild allergy to severe anaphylactic reactions. Curr Opin Allergy Clin Immunol. 2008 Jun; 8(3):261-265. 18560303
10. Sicherer SH, Muñoz-Furlong A, Godbold JH, Sampson HA. US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol. 2010; 125(6):1322-1326. 20462634
11. De Knop KJ, Verweij MM, Grimmelikhuijsen M, et al. Age-related sensitization profiles for hazelnut (Corylus avellana) in a birch-endemic region. Pediatr Allergy Immunol. 2011 Feb; 22(1Pt 2):e139-149. 21342279
12. Masthoff LJ, van Hoffen E, de Reus A, et al. Hazelnut allergy differs between children and adults in frequency of severity, aetiology and relevance of diagnostic parameters. Clin Exp Allergy. 2014 Dec; 44(12):1539-1545. 25333730
13. Flinterman AE, Akkerdaas JH, den Hartog Jager CF, et al. Lipid transfer protein-linked hazelnut allergy in children from a non-Mediterranean birch-endemic area. J Allergy Clin Immunol. 2008 Feb; 121(2):423-428. 18036652
14. Faber MA, De Graag M, Van Der Heijden C, et al. Cor a 14: Missing link in the molecular diagnosis of hazelnut allergy? Int Arch Allergy Immunol. 2014; 164(3):200-206. 25034302
15. Garino C, Zuidmeer L, Marsh J, et al. Isolation, cloning, and characterization of the 2S albumin: a new allergen from hazelnut. Mol Nutr Food Res. 2010 Sep; 54(9):1257-1265. 20373288
16. Verweij MM, Hagendorens MM, De Knop KJ, et al. Young infants with atopic dermatitis can display sensitization to Cor a 9, an 11S legumin-like seed-storage protein from hazelnut (Corylus avellana). Pediatr Allergy Immunol. 2011 Mar; 22(2):196-201. 20579306
17. Eller E, Mortz CG, Bindslev-Jensen C. Cor a 14 is the superior serological marker for hazelnut allergy in children, independent of concomitant peanut allergy. Allergy. 2015 Dec 15. doi: 10.1111/all.12820. 26666993
18. Beyer K, Grabenhenrich L, Härtl M, et al. Predictive values of component-specific IgE for the outcome of peanut and hazelnut food challenges in children. Allergy. 2015 Jan; 70(1):90-98. 25308885
19. Kattan JD, Sicherer SH, Sampson HA. Clinical reactivity to hazelnut may be better identified by component testing than traditional testing methods. J Allergy Clin Immunol Pract. 2014. 2(5): p. 633-634 e1.
20. Masthoff LJ, Mattsson L, Zuidmeer-Jongejan L, et al. Sensitization to Cor a 9 and Cor a 14 is highly specific for a severe hazelnut allergy in Dutch children and adults. J Allergy Clin Immunol. 2013 Aug; 132(2):393-399. 23582909
21. Carraro S, Berardi M, Bozzetto S, Baraldi E, Zanconato S. COR a 14-specific IgE predicts symptomatic hazelnut allergy in children. Pediatr Allergy Immunol. 2015 Dec 17. doi: 10.1111/pai.12526. 26680531
22. Datema MR, Zuidmeer-Jongejan L, Asero R, et al. Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey. J Allergy Clin Immunol. 2015 Aug; 136(2):382-391. 25772593
23. Asero R, Mistrello G, Roncarolo D, Amato S. Walnut-induced anaphylaxis with cross-reactivity to hazelnut and Brazil nut. J Allergy Clin Immunol. 2004 Feb; 113(2):358-360. 14767457
24. Ebo DG, Verweij MM, Sabato V, Hagendorens MM, Bridts CH, De Clerck LS. Hazelnut allergy: A multi-faced condition with demographic and geographic characteristics. Acta Clin Belg. 2012 Sep-Oct; 67(5):317-321. 23189537
25. Uotila R, Kukkonen AK, Pelkonen A, Mäkelä MJ. Cross-sensitization profiles of edible nuts in a birch-endemic area. Allergy. 2015 Dec 25. doi: 10.1111/all. 12826. 26706253
26. Hansen KS, Ballmer-Weber BK, Lüttkopf D, et al. Roasted hazelnuts—allergenic activity evaluated by double-blind, placebo-controlled food challenge. Allergy. 2003 Feb; 58(2):132-138. 12622744
27. Werfel T, Asero R, Ballmer-Weber BK, et al. Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens. Allergy. 2015 Sep; 70(9):1079-1090. 26095197
28. Egger M, Hauser M, Mari A, Ferreira F, Gadermaier G. The role of lipid transfer proteins in allergic diseases. Curr Allergy Asthma Rep. 2010 Sep; 10(5):326-335. 20582490
29. Hartz C, Lauer I, del Mar San Miguel Moncin M, et al. Comparison of IgE-binding capacity, cross-reactivity and biological potency of allergenic non-specific lipidtransfer proteins from peach, cherry and hazelnut. Int Arch Allergy Immunol. 2010; 153(4):335-346. 20558999
30. Schulten V, Nagl B, Scala E, et al. Pru p 3, the nonspecific lipid transfer protein from peach, dominates the immune response to its homolog in hazelnut. Allergy. 2011 Aug; 66(8):1005-1013. 21352239
31. Schocker F, Lüttkopf D, Scheurer S, et al. Recombinant lipid transfer protein Cor a 8 from hazelnut: a new tool for in vitro diagnosis of potentially severe hazelnut allergy. J Allergy Clin Immunol. 2004 Jan; 113(1):141-147. 14713920
32. Hansen KS, Ballmer-Weber BK, Sastre J, et al. Component-resolved in vitro diagnosis of hazelnut allergy in Europe. J Allergy Clin Immunol. 2009 May; 123(5):1134-1141. 19344939
33. Verweij MM, Hagendorens MM, Trashin S, et al. Age-dependent sensitization to the 7S-vicilin-like protein Cor a 11 from hazelnut (Corylus avellana) in a birch-endemic region. J Investig Allergol Clin Immunol. 2012; 22(4):245-251. 22812192

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
604734 IgE Hazelnut w/Component Rflx 602444 Class Description N/A
604734 IgE Hazelnut w/Component Rflx 602483 F017-IgE Hazelnut (Filbert) kU/L 6136-6
Reflex Table for F017-IgE Hazelnut (Filbert)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 602444 Class Description 602444 Class Description N/A
Reflex Table for F017-IgE Hazelnut (Filbert)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 604726 Panel 604726 604735 F428-IgE Cor a 1 kU/L 69421-6
Reflex 2 000000 602444 000000 N/A
Reflex Table for F017-IgE Hazelnut (Filbert)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 604726 Panel 604726 604741 F425-IgE Cor a 8 kU/L 58753-5
Reflex 2 000000 602444 000000 N/A
Reflex Table for F017-IgE Hazelnut (Filbert)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 604726 Panel 604726 604742 F440-IgE Cor a 9 kU/L 65765-0
Reflex 2 000000 602444 000000 N/A
Reflex Table for F017-IgE Hazelnut (Filbert)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 604726 Panel 604726 604743 F439-IgE Cor a 14 kU/L 81788-2
Reflex 2 000000 602444 000000 N/A
Reflex Table for F017-IgE Hazelnut (Filbert)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 604726 Panel 604726 603850 Reflex Allergy Tracking N/A

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