Evaluation of patients with suspected hazelnut-food allergy
The determination of the relative amount of IgE antibody to total hazelnut-food, and IgE antibodies to specific hazelnut-food components, may aid in assessment of the potential strength and type of allergenic response to hazelnut-food.
IgE antibody to total hazelnut-food will be initially tested.
If detectable total specific hazelnut-food IgE antibody is present, additional component hazelnut-food allergen antibody testing will be performed. This is comprised of testing for IgE antibodies to the potential allergens Cor a 1, Cor a 8, Cor a 9, and Cor a 14.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| NUTHX | Hazelnut-Food Components, IgE, S | No | No |
Testing begins with analysis of hazelnut-food-specific total IgE. If hazelnut food-specific total IgE is negative (<0.10 kU/L), testing is complete.
If hazelnut food-specific total IgE is 0.10 kU/L or more, then the four hazelnut-food components (Cor a 1, Cor a 8, Cor a 9, and Cor a 14) will be performed at an additional charge.
Fluorescent Enzyme Immunoassay (FEIA)
Hazelnut-Food components
Cor a 1
Cor a 8
Cor a 9
Cor a 14
Testing begins with analysis of hazelnut-food-specific total IgE. If hazelnut food-specific total IgE is negative (<0.10 kU/L), testing is complete.
If hazelnut food-specific total IgE is 0.10 kU/L or more, then the four hazelnut-food components (Cor a 1, Cor a 8, Cor a 9, and Cor a 14) will be performed at an additional charge.
Serum
For a listing of allergens available for testing, see Allergens - Immunoglobulin E (IgE) Antibodies.
Collection 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.
If not ordering electronically, complete, print, and send an Allergen Test Request (T236) with the specimen.
0.6 mL
| Gross hemolysis | OK |
| Gross lipemia | OK |
| Gross icterus | OK |
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 14 days | |
| Frozen | 90 days |
Evaluation of patients with suspected hazelnut-food allergy
Testing begins with analysis of hazelnut-food-specific total IgE. If hazelnut food-specific total IgE is negative (<0.10 kU/L), testing is complete.
If hazelnut food-specific total IgE is 0.10 kU/L or more, then the four hazelnut-food components (Cor a 1, Cor a 8, Cor a 9, and Cor a 14) will be 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 components 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 to 11S 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 predictor 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).
| Class | IgE kU/L | Interpretation |
| 0 | <0.10 | Negative |
| 0/1 | 0.10-0.34 | Borderline/Equivocal |
| 1 | 0.35-0.69 | Equivocal |
| 2 | 0.70-3.49 | Positive |
| 3 | 3.50-17.4 | Positive |
| 4 | 17.5-49.9 | Strongly positive |
| 5 | 50.0-99.9 | Strongly positive |
| 6 | > or =100 | Strongly positive |
Concentrations of 0.70 kU/L or more (class 2 and above) will flag as abnormally high.
Reference values apply to all ages.
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. Negative IgE results for total hazelnut-food antibody may indicate a lack of sensitization to 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.
Positive results for IgE to hazelnut or any potential hazelnut allergenic components are not diagnostic for allergy and only indicate patient may be sensitized to hazelnut 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 hazelnut specific IgE testing.
1. Salo PM, Arbes SJ Jr, Jaramillo R, et al. Prevalence of allergic sensitization in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. J Allergy Clin Immunol. 2014;134(2):350-359
2. Waserman S, Watson W. Food allergy. Allergy Asthma Clin Immunol. 2011;7 Suppl 1(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
5. Lomas JM, Jarvinen KM. Managing nut-induced anaphylaxis: challenges and solutions. J Asthma Allergy. 2015;8:115-123
6. Maloney JM, 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
7. Sicherer SH, Burks AW, Sampson HA. Clinical features of acute allergic reactions to peanut and tree nuts in children. Pediatrics. 1998;102(1):e6
8. Crespo JF, James JM, Fernandez-Rodriguez C, Rodriguez J. Food allergy: nuts and tree nuts [published correction appears in Br J Nutr. 2008 Feb;99(2):447-8]. Br J Nutr. 2006;96 Suppl 2:S95-S102
9. Yang L, Clements S, Joks R. A retrospective study of peanut and tree nut allergy: Sensitization and correlations with clinical manifestations [published online ahead of print, 2015 Feb 27]. Allergy Rhinol (Providence). 2015; doi:10.2500/ar.20105.6.0108
10. Masthoff LJ, 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 Clin Belg. 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 [published correction appears in Allergy. 2020 Aug;75(8):2145-2145]. 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. J Allergy Clin Immunol. 2013;131(5):1384-92.e6
16. Nilsson C, Berthold M, Mascialino B, Orme M, Sjolander S, Hamilton R. Allergen components in diagnosing childhood hazelnut allergy: Systematic literature review and meta-analysis. Pediatr Allergy Immunol. 2020;31(2):186-196
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
23. Masthoff LJ, van Hoffen E, Mattsson L, et al. Peanut allergy is common among hazelnut-sensitized subjects but is not primarily the result of IgE cross-reactivity. Allergy. 2015;70(3):265-274
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, Mäkelä 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)
Monday through Friday
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.
86003
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| NUTHR | Hazelnut-Food Component Reflex, S | 6136-6 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| NUTH1 | Hazelnut-Food, IgE, S | 6136-6 |