Allergen Profile, Peanut, IgE With Component Reflexes

CPT: 86003. If reflex testing is performed, concomitant CPT codes/charges will apply.
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Test Details

Test Includes

Peanut (whole); Reflex criteria: If peanut (whole) IgE ≥0.10 kU/L, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9 will be performed.

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).1-5 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 systemic allergic reactions versus those who are sensitized but clinically tolerant. CDR 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. Alternatively, allergies to plant derived foods may occur in pollen sensitized individuals due to pollen allergens that cross react with food allergens. 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:1-5

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

• Improve the risk assessment using allergen components

• Improve management of allergic patients

Limitations

Allergen-specific IgE assays do not demonstrate absolute positive and negative predictive values for allergic disease. Clinical history must be incorporated into the diagnostic determination. Although the use of component resolved IgE testing may enhance the evaluation of potentially allergic individuals over the use of whole extracts alone, it cannot yet replace clinical history and oral food challenge in most cases. Sensitization against thus far unidentified determinants that are not found in the whole extract our in components might cause symptoms in rare cases.

Methodology

Thermo Fisher ImmunoCAP® Allergen-specific IgE

Additional Information

Peanut.While sensitization to peanut is common, with somewhere between 8% and 12% of the general public showing sensitivity on either skin prick test or peanut extract allergen specific IgE testing, the majority of these people are not allergic.6-11

Peanut Components

Ara h 1

Ara h 2

Ara h 3

• Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood.16

• IgE to Ara h 2 has the best discriminative ability of all diagnostic tests for peanut allergy. It can accurately diagnose peanut allergy in 28% of patients but cannot be used to exclude a peanut allergy in an adult population.6,12-16

• The presence of antibodies to Ara h 1 and/or Ara h 3 increases the risk of severe reactions.8,12,14,13,17-24

• These three major peanut allergens (Ara h 1, Ara h 2 and Ara h 3) contain similar peptide sequences accounting for the high extent of cross-reactivity observed among them.25

• Ara h 1, Ara h 2 and Ara h 3 have been associated with severe symptoms, although anaphylactic reactions have been described in patients negative for these allergens.6

• Reactivity to these dominant allergens at the time of diagnosis in a population of North American infants and toddlers with early-onset peanut allergy was found to be associated with future allergy persistence at age 13 years.26

Ara h 8

• IgE antibodies to the Ara h 8 are seldom associated with systemic reactions but more often to local reactions like oral allergy syndrome.16,21,27-31

• Birch-sensitized individuals are frequently co-sensitized to peanut Ara h 8.31

• Sensitization to this birch pollen cross-reactive allergen varies depending on local exposure to birch pollen.21,29,31

• Children that are mono-sensitized to Ara h 8 can usually safely ingest peanut.28

Ara h 9

• Ara h 9 is a minor component of peanuts.34 However, sensitization to this type of allergenic protein, referred to as a Lipid Transfer Protein, is generally associated with severe reactions in addition to OAS.32-35

• Ara h 9 has been correlated with mild to severe symptoms in Mediterranean patients (Vareeda, Ballmer-Weber).

General Comments

• The heterogeneity in the clinical and immunological phenotype of peanut allergy in distinct geographical areas reflect exposures to different environmental pollen and differences in dietary traditions.16,36

• The most commonly occurring sensitization to peanut proteins in individuals who tolerate peanut is directed to Ara h 8 and Ara h 9.16

• Use of component testing allows for the assessment of sensitization to proteins that may be under-represented in whole peanut extracts.36

Link for further information on peanut CDR.

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. Chokshi NY, Sicherer SH. Interpreting IgE sensitization tests in food allergy. Expert Rev Clin Immunol. 2015 Dec;1-15. 26666347
2. 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
3. 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
4. Sampson HA, Aceves S, Bock SA, et al. Food allergy: A practice parameter update−2014. J Allergy Clin Immunol. 2014; 134(5):1016-1025.e43. 25174862
5. Kattan JD, Sicherer SH. Optimizing the diagnosis of food allergy. Immunol Allergy Clin North Am. 2015 Feb; 35(1):61-76. 25459577
6. Sicherer SH, Wood RA. Advances in diagnosing peanut allergy. J Allergy Clin Immunol Pract. 2013 Jan; 1(1):1–13. 24229816
7. Nicolaou N, Poorafshar M, Murray C, et al. Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component-resolved diagnostics. J Allergy Clin Immunol. 2010 Jan;125(1):191–197. 20109746
8. Nicolaou N, Custovic A. Molecular diagnosis of peanut and legume allergy. Curr Opin Allergy Clin Immunol. 2011 Jun; 11(3):222-228. 21464707
9. Mortz CG, Andersen KE, Bindslev-Jensen C. The prevalence of peanut sensitization and the association to pollen sensitization in a cohort of unselected adolescents--The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS). Pediatr Allergy Immunol. 2005 Sep; 16(6):501-506. 16176397
10. Tariq SM, Stevens M, Matthews S, Ridout S, Twiselton R, Hide DW. Cohort study of peanut and tree nut sensitisation by age of 4 years. BMJ. 1996 Aug 31; 313(7056):514-517. 8789974
11. Moneret-Vautrin DA, Morisset M, Flabbee J, Beaudouin E, Kanny G. Epidemiology of life-threatening and lethal anaphylaxis: A review. Allergy. 2005 Apr; 60(4):443-451. 15727574
12. Klemans RJ, Broekman HC, Knol EF, et al. Ara h 2 is the best predictor for peanut allergy in adults. J Allergy Clin Immunol Pract. 2013 Nov-Dec; 1(6):632-638. 24565711
13. Eller E, Bindslev-Jensen C. Clinical value of component-resolved diagnostics in peanut-allergic patients. Allergy. 2013 Feb; 68(2):190-194. 23240588
14. Dang TD, Tang M, Choo S, et al. Increasing the accuracy of peanut allergy diagnosis by using Ara h 2. J Allergy Clin Immunol. 2012 Apr; 129(4):1056-1063. 22385632
15. Beyer K, Grabenhenrich L, Hartl 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
16. Ballmer-Weber BK, Lidholm J, Fernández-Rivas M, et al. IgE recognition patterns in peanut allergy are age dependent: Perspectives of the EuroPrevall study. Allergy. 2015 Apr; 70(4):391-407. 25620497
17. Peeters KA, Koppelman SJ, van Hoffen E, et al. Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy? Clin Exp Allergy. 2007 Jan; 37(1):108-115. 17210048
18. Astier C, Morisset M, Roitel O, et al. Predictive value of skin prick tests using recombinant allergens for diagnosis of peanut allergy. J Allergy Clin Immunol. 2006 Jul; 118(1):250-256. 16815163
19. Flinterman AE, van Hoffen E, den Hartog Jager CF, et al. Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time. Clin Exp Allergy. 2007 Aug; 37(8):1221-1228. 17651153
20. Codreanu F, Collignon O, Roitel O, et al. A novel immunoassay using recombinant allergens simplifies peanut allergy diagnosis. Int Arch Allergy Immunol. 2011; 154(3):216-226. 20861643
21. Lange L, Beyer K, Kleine-Tebbe J. Benefits and limitations of molecular diagnostics in peanut allergy: Part 14 of the series Molecular Allergology. Allergo J Int. 2014; 23(5):158-163. 26120527
22. Keet CA, Johnson K, Savage JH, Hamilton RG, Wood RA. Evaluation of Ara h2 IgE thresholds in the diagnosis of peanut allergy in a clinical population. J Allergy Clin Immunol Pract. 2013 Jan; 1(1):101-103. 24229831
23. Lieberman JA, Glaumann S, Batelson S, Borres MP, Sampson HA, Nilsson C. The utility of peanut components in the diagnosis of IgE-mediated peanut allergy among distinct populations. J Allergy Clin Immunol Pract. 2013 Jan; 1(1):75-82. 24229825
24. Movérare R, Ahlstedt S, Bengtsson U, et al. Evaluation of IgE antibodies to recombinant peanut allergens in patients with reported reactions to peanut. Int Arch Allergy Immunol. 2011; 156(3):282-290. 21720173
25. Bublin M, Kostadinova M, Radauer C, et al. IgE cross-reactivity between the major peanut allergen Ara h 2 and the nonhomologous allergens Ara h 1 and Arah 3. J Allergy Clin Immunol. 2013 Jul; 132(1):118-124. 23465659
26. Bégin P, Vitte J, Paradis L, et al. Long-term prognostic value of component-resolved diagnosis in infants and toddlers with peanut allergy. Pediatr Allergy Immunol. 2014 Aug; 25(5):506-508. 24641729
27. Asarnoj A, Movérare R, Ostblom E, et al. IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds. Allergy. 2010 Sep; 65(9):1189-1195. 20146729
28. Asarnoj A, Nilsson C, Lidholm J, et al. Peanut component Ara h 8 sensitization and tolerance to peanut. J Allergy Clin Immunol. 2012 Aug; 130(2):468-472. 22738678
29. Mittag D, Akkerdaas J, Ballmer-Weber BK, et al. Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy. J Allergy Clin Immunol. 2004 Dec; 114(6):1410-1417. 15577846
30. Asarnoj A, Ostblom E, Ahlstedt S, et al. Reported symptoms to peanut between 4 and 8 years among children sensitized to peanut and birch pollen -results from the BAMSE birth cohort. Allergy. 2010 Feb; 65(2):213-219. 19712120
31. 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
32. 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
33. Lauer I, Dueringer N, Pokoj S, et al. The non-specific lipid transfer protein, Ara h 9, is an important allergen in peanut. Clin Exp Allergy. 2009 Sep; 39(9):1427-1437. 19624524
34. Krause S, Reese G, Randow S, et al. Lipid transfer protein (Ara h 9) as a new peanut allergen relevant for a Mediterranean allergic population. J Allergy Clin Immunol. 2009 Oct; 124(4):771-778.e5 19665774
35. Vereda A, van Hage M, Ahlstedt S, et al. Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions. J Allergy Clin Immunol. 2011 Mar; 127(3):603-607. 21093026
36. Aalberse JA, Meijer Y, Derksen N, van der Palen-Merkus T, Knol E, Aalberse RC. Moving from peanut extract to peanut components: towards validation of component-resolved IgE tests. Allergy. 2013 Jun; 68(6):748-756. 23621551

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
603916 IgE Peanut w/Component Reflex 602444 Class Description N/A
603916 IgE Peanut w/Component Reflex 602451 F013-IgE Peanut kU/L 6206-7
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 602444 Class Description 602444 Class Description N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603835 F422-IgE Ara h 1 kU/L 58779-0
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603836 F423-IgE Ara h 2 kU/L 58778-2
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603838 F424-IgE Ara h 3 kU/L 58777-4
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603839 F352-IgE Ara h 8 kU/L 63477-4
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603840 F427-IgE Ara h 9 kU/L 64965-7
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603850 Reflex Allergy Tracking N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603835 F422-IgE Ara h 1 kU/L 58779-0
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603836 F423-IgE Ara h 2 kU/L 58778-2
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603838 F424-IgE Ara h 3 kU/L 58777-4
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603839 F352-IgE Ara h 8 kU/L 63477-4
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603840 F427-IgE Ara h 9 kU/L 64965-7
Reflex 2 000000 602444 000000 N/A
Reflex Table for F013-IgE Peanut
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603847 Panel 603847 603850 Reflex Allergy Tracking N/A

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