Test Id : NUTHX

If hazelnut-food specific total IgE is 0.10 kU/L or more, then testing for four hazelnut-food components (Cor a 1, Cor a 8, Cor a 9, Cor a 14) is performed at an additional charge.

Only orderable as a reflex. For more information see NUTHR / Hazelnut-Food, IgE with Reflex to Hazelnut-Food Components, IgE, Serum.

Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

0.6 mL

Evaluation of patients with suspected hazelnut-food allergy to one of 4 hazelnut-food components

If hazelnut-food specific total IgE is 0.10 kU/L or more, then testing for four hazelnut-food components (Cor a 1, Cor a 8, Cor a 9, Cor a 14) is performed at an additional charge.

Allergies to tree nuts are relatively prevalent and can result in severe reactions. The main culprits in tree nut allergies include walnut, almond, pistachio, cashew, pecan, hazelnut, macadamia, Brazil nut, and pine nuts. Tree nut allergy often appears in young children and estimates of prevalence range from 0.1% to greater than 5% of the population, dependent on geographical region.

In the case of nut-induced allergic reactions, as with many other foods, symptoms usually present within minutes of ingestion. Over 80% of reactions to tree nuts involve allergy related respiratory symptoms. Tree nut allergies are one of the most dangerous types of allergic reaction with 20% to 40% of cases of related anaphylaxis and 70% to 90% of fatalities attributable to nut exposure, including peanut exposure.

Hazelnut allergy can occur upon ingestion as a systemic food allergy that can be associated with severe reactions or as oral allergy syndrome, often associated with pollen allergy (pollen-food allergy syndrome). It is the most common tree nut allergy in Europe. Sensitization to birch pollen is strongly associated with hazelnut sensitization with 84% of those with birch pollen allergy being sensitized to hazelnuts.

Components of hazelnut allergy can be used to stratify risk of severe systemic reactions. Hazelnut allergy can be severe or can be pollen related and less severe. The component protein Cor a 1 is heat and digestion labile and is often cross-reactive with birch pollen sensitivity due to cross-reactivity between homologous allergens of hazelnut and birch pollens (PR-10 proteins Cor a 1 and Bet v 1). Sensitization to Cor a 1 component protein is mainly associated with local reactions posing a lower risk of severe systemic reaction. Pollen-related hazelnut allergy is often observed in adults, with symptoms limited to the oropharyngeal cavity. However, systemic symptoms and even anaphylaxis have been infrequently reported with sensitivity to Cor a 1.

Cor a 8 is a heat and digestion stabile nonspecific lipid transfer protein that exhibits sensitization in 8% to 17% of hazelnut allergy cases in the United States, with high prevalence in areas that lack birch trees. Cor a 8 sensitization can be associated with clinically silent hazelnut tolerant individuals, oral allergy syndrome or in some cases severe allergy. Peach allergy may be associated with sensitivity for Cor a 8.

Cor a 9 and 14 are heat and digestion stable protein component that are associated with higher risks or severe, systemic reaction. Cor a 9 and Cor a 14 sensitization serve as excellent diagnostic markers for identifying direct hazelnut allergy and for prediction of potentially severe symptoms. Sensitization to Cor a 9 (a legume like globulin) was observed in 10% of hazelnut allergic individuals and has been established to be associated with severe systemic reactions. Other studies have put the sensitization rate or Cor a 9 to be as much as 35%. Cor a 9 may show crossreactivity to11S globulin protein components of walnut (Jug r 4), peanut (Ara h 3), Brazil nut (Ber e 2), soybean (Gly m 6), cashew (Ana o 2), almond (Pru du 6) and pistachio (Pis v 2).  Sensitization to Cor a 14 (a 2S albumin allergen) has been observed in 6% of allergic individuals and is associated with moderate and severe systemic reactions. Cor a 14 is highly heat and digestion resistant and serves as an excellent prediction for clinical allergy. Cor a 14 sensitization has been reported in 15% of individuals with severe symptoms, 5.6% of individuals with moderate symptoms, and 4% of those with localized symptoms. Its cross reactivity is limited to walnut (Jug r 1) and pecan (Car i 1) protein components. Cor a 14-sIgE determination was a better predictor of oral food challenge sensitivity than other hazelnut component allergens (Cor a 1, Cor a 8 and Cor a 9).

Only orderable as a reflex. For more information see NUTHR / Hazelnut-Food, IgE with Reflex to Hazelnut-Food Components, IgE, Serum.

Concentrations of 0.70 kU/L or more (class 2 and above) will flag as abnormally high.

Reference values apply to all ages.

When detectable total hazelnut-food IgE antibody is present (> or =0.10 IgE kUa/L), additional specific component IgE antibody testing will be performed. If a potential specific allergenic hazelnut-food component IgE is detectable (> or =0.10 IgE kUa/L), an interpretive report will be provided.

When the sample is negative for total hazelnut-food IgE antibody (<0.10 IgE kUa/L), further testing for specific hazelnut-food component IgE antibodies will not be performed. A negative IgE result for total cashew antibody may indicate a lack of sensitization to the potential hazelnut-food allergenic components.

Clinical correlation of results from in vitro IgE testing with patient history of allergic or anaphylactic responses to hazelnut is recommended.

Negative results for IgE antibodies to hazelnut or allergenic components do not completely exclude the possibility of clinically relevant allergic responses upon exposure.

Positive results for IgE antibodies to hazelnut or any potential hazelnut- allergenic components are not diagnostic for allergy and only indicate patient may be sensitized to hazelnut-food or a cross-reactive allergen.

Testing for IgE antibodies may not be useful in patients previously treated with immunotherapy to determine if residual clinical sensitivity exists or in patients whose medical management does not depend upon the identification of allergen specificity.

False-positive results for IgE antibodies may occur in patients with markedly elevated serum IgE (>2500 kU/L) due to nonspecific binding to allergen solid phases.

Cross-reacting carbohydrate determinants may also result in positive total walnut specific IgE testing.

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2. Waserman S, Watson W. Food allergy. Allergy Asthma & Clin Immuno.2011, 7 Suppl1 (Suppl 1):S7

3. Abrams EM, Sicherer SH. Diagnosis and management of food allergy. CMAJ. 2016;188(15):1087–1093

4. Weinberger T, Sicherer S. Current perspectives on tree nut allergy: a review. J Asthma Allergy. 2018;11:41–51

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6. Maloney J, Rudengren M, Ahlstedt S, Bock SA, Sampson HA. The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy. J Allergy Clin Immunol. 2008;122(1):145-151

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10. Masthoff L, Hoff R, Verhoeckx KC, et al. A systematic review of the effect of thermal processing on the allergenicity of tree nuts. Allergy 2013;68(8):983-993

11. 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 clinica Belgica. 2012;67(5):317-321

12 .Calamelli E, Trozzo A, Di Blasi E, Serra L, Bottau P. Hazelnut allergy. Medicina (Kaunas). 2021;57(1):67

13. Uotila R, Kukkonen AK, Pelkonen AS, Makela MJ. Cross-sensitization profiles of edible nuts in a birch-endemic area. Allergy. 2016;71(4):514-521

14. Datema MR, van Ree R, Asero R, et al. Component-resolved diagnosis and beyond: Multivariable regression models to predict severity of hazelnut allergy. Allergy. 2018;73(3):549-559

15. Hofmann C, Scheurer S, Rost K, et al. Cor a 1-reactive T cells and IgE are predominantly cross-reactive to Bet v 1 in patients with birch pollen-associated food allergy to hazelnut. The J Allergy Clin Immunol. 2013;131(5):1384-1392.e6

16. Nilsson C, Berthold M, Mascialino B, Orme M, Sjölander S, Hamilton R. Allergen components in diagnosing childhood hazelnut allergy: Systematic literature review and meta-analysis. Pediatr Allergy Immunol. 2020;31(2):186-96.

17. Inoue Y, Sato S, Takahashi K, et al. Component-resolved diagnostics can be useful for identifying hazelnut allergy in Japanese children. Allergol Int. 2020;69(2):239-245

18. 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

19. Costa J, Mafra I, Carrapatoso I, Oliveira MB. Hazelnut allergens: Molecular characterization, detection, and clinical relevance. Crit Rev Food Sci Nutr. 2016;56(15):2579-2605

20. Buyuktiryaki B, Cavkaytar O, Sahiner UM, et al. Cor a 14, hazelnut-specific IgE, and SPT as a reliable tool in hazelnut allergy diagnosis in Eastern Mediterranean Children. J Allergy Clin Immunol Pract. 2016;4(2):265-72.e3

21. Brough HA, Caubet JC, Mazon A, et al. Defining challenge-proven coexistent nut and sesame seed allergy: A prospective multicenter European study. J Allergy Clin Immunol. 2020;145(4):1231-1239

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;136(2):382-391

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24. Bastiaan-Net S, Batstra MR, Aazamy N, et al. IgE cross-reactivity measurement of cashew nut, hazelnut and peanut using a novel IMMULITE inhibition method. Clin Chem Lab Med. 2020;58(11):1875-1883

25. Carraro S, Berardi M, Bozzetto S, Baraldi E, Zanconato S. COR a 14-specific IgE predicts symptomatic hazelnut allergy in children. Pediatr Allergy Immunol. 2016;27(3):322-324

26. Buyuktiryaki B, Cavkaytar O, Sahiner UM, et al. Cor a 14, hazelnut-specific IgE, and SPT as a reliable tool in hazelnut allergy diagnosis in Eastern Mediterranean children. J Allergy Clin Immunol Pract. 2016;4(2):265-72.e3

27. Uotila R, Rontynen P, Pelkonen AS, Voutilainen H, Kaarina Kukkonen A, Makela MJ. For hazelnut allergy, component testing of Cor a 9 and Cor a 14 is relevant also in birch-endemic areas. Allergy. 2020;75(11):2977-2980

Specific IgE from the patient's serum reacts with the allergen of interest, which is covalently coupled to an ImmunoCAP. After washing away nonspecific IgE, enzyme-labeled anti-IgE antibody is added to form a complex. After incubation, unbound anti-IgE is washed away, and the bound complex is then incubated with a developing agent. After stopping the reaction, the fluorescence of the eluate is measured. Fluorescence is proportional to the amount of specific IgE present in the patient's sample (ie, the higher the fluorescence value, the more IgE antibody is present).(Package insert: ImmunoCAP System Specific IgE FEIA. Phadia: Rev 06/2020)

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This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

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