Allergen Profile, Milk, IgE With Component Reflexes

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

Milk; Reflex criteria: If milk IgE ≥0.35 kU/L, α-lactalbumin, β-lactoglobulin, and casein IgE will be performed.


Expected Turnaround Time

3 - 4 days


Related Documents

For more information, please view the literature below.

Food Component Allergen Testing Services


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


Test Details


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).1-4 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.


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 or in components might cause symptoms in rare cases.


Methodology

Thermo Fisher ImmunoCAP® Allergen-specific IgE


Additional Information

Cow's Milk Allergy

Cow's milk allergy is the most common food allergy in early childhood and affects about 2.5% of infants during their first years of life5-7 with symptoms ranging from relatively mild to severe and life-threatening.8 Egg allergy can cause severe allergic reactions in sensitized children, and egg avoidance can cause significant dietary limitations. Although most infants outgrow cow’s milk allergy by age three, it can become persistent in a minority of children. Cow’s milk allergy is associated with an increased risk of development of other allergic disorders, such as allergic asthma, atopic eczema, rhinoconjunctivitis, or egg allergy.9

Approximately 75% of children with cow’s milk allergy react to fresh milk and tolerate extensively heated cow’s milk.10

Cow's Milk Components

Bos d 8, Casein

• 80% of the milk protein content is casein (Bos d 8).11

• Bos d 8 is relatively stable to heat and retains its allergenicity after extensive heating.10,11

• The levels of Bos d 8 IgE antibodies reflect the severity of the milk allergy.12-15

• High levels of Bos d 8 IgE antibodies indicate allergy to both fresh and baked milk.16

• Low or undetectable levels of Bos d 8 IgE antibodies indicate tolerance to baked milk products, eg, cakes and cookies.16

• Patients sensitized to Bos d 8 are also at risk of severe reactions upon intake of nondairy products in which casein may be used as an additive (eg, in sausages, chocolate, and potato chips).17,18

• Children often outgrow their milk allergy—early signs of tolerance development can be detected by tracking the reduction in cow’s milk IgE (extract)19,20 and/or the component Bos d 8 IgE levels over time.15,21-23

• Quantifying IgE levels to Bos d 8 can help determine if a challenge test should be performed.24-26

Bos d 4, α-lactalbumin

Bos d 5, β-lactoglobulin

• Whey proteins make up twenty percent of the protein in milk.11 Whey proteins include α–lactalbumin (Bos d 4) and β–lactoglobulin (Bos d 5)11

• Whey proteins Bos d 4 and Bos d 5 are rather heat labile and, therefore, destroyed by cooking.11

• Patients sensitized to Bos d 4 and Bos d 5 but with low levels of IgE to Bos d 8 may tolerate baked milk products.12,15,27,28

• As tolerance develops, decreasing levels of IgE to Bos d 4 and Bos d 5 are also often observed.21

Link for further information on milk CRD.


Footnotes

1. 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
2. Chokshi NY, Sicherer SH. Interpreting IgE sensitization tests in food allergy. Expert Rev Clin Immunol. 2015:1-15. 26666347
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. Sastre J. Molecular diagnosis in allergy. Clin Exp Allergy. 2010 Oct; 40(1):1442-1460. 20682003
5. Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014 Feb; 133(2):291-307. 24388012
6. Tsabouri S, Douros K, Priftis KN. Cow's milk allergenicity. Endocr Metab Immune Disord Drug Targets. 2014 Mar; 14(1):16-26. 24450454
7. Wood RA, Sicherer SH, Vickery BP, et al. The natural history of milk allergy in an observational cohort. J Allergy Clin Immunol. 2013 Mar; 131(3):805-812. 23273958
8. Benhamou AH, Schäppi Tempia MG, Belli DC, Eigenmann PA. An overview of cow's milk allergy in children. Swiss Med Wkly. 2009 May 30; 139(21-22):300-307. 19492195
9. Saarinen KM, Pelkonen AS, Mäkelä MJ, Savilahti E. Clinical course and prognosis of cow's milk allergy are dependent on milk-specific IgE status. J Allergy Clin Immunol. 2005 Oct; 116(4):869-875. 16210063
10. Nowak-Wegrzyn A, Bloom KA, Sicherer SH, et al. Tolerance to extensively heated milk in children with cow's milk allergy. J Allergy Clin Immunol. 2008 Aug; 122(2):342-347. 18620743
11. Wal JM. Bovine milk allergenicity. Ann Allergy Asthma Immunol. 2004 Nov; 93(5 Suppl 3):S2-11. 15562868
12. García-Ara MC, Boyano-Martínez MT, Díaz-Pena JM, Martín-Muñoz MF, Martín-Esteban M. Cow's milk-specific immunoglobulin E levels as predictors of clinical reactivity in the follow-up of the cow's milk allergy infants. Clin Exp Allergy. 2004 Jun; 34(6):866-870. 15196272
13. Docena GH, Fernández R, Chirdo FG, Fossati CA. Identification of casein as the major allergenic and antigenic protein of cow’s milk. Allergy. 1996 Jun; 51(6): 412–416. 8837665
14. Shek LP, Bardina L, Castro R, Sampson HA, Beyer K. Humoral and cellular responses to cow milk proteins in patients with milk-induced IgE-mediated and non-IgE-mediated disorders. Allergy. 2005 Jul; 60(7):912-919. 15932382
15. Ito K, Futamura M, Movérare R, et al. The usefulness of casein specific IgE and IgG4 antibodies in cow’s milk allergic children. Clin Mol Allergy. 2012 Jan 2; 10(1):1. 22212305
16. Caubet JC, Nowak-Wegrzyn A, Moshier E, Godbold J, Wang J, Sampson HA. Utility of casein specific IgE levels in predicting reactivity to baked milk. J Allergy Clin Immunol. 2013 Jan; 131(1):222–224. 22921870
17. Gern JE, Yang E, Evrard HM, Sampson HA. Allergic reactions to milk-contaminated "nondairy" products. N Engl J Med. 1991 Apr 4; 324(14):976-979. 2002820
18. Boyano-Martínez T, García-Ara C, Pedrosa M, Diaz-Pena JM, Quirce S. Accidental allergic reactions in children allergic to cow's milk proteins. J Allergy Clin Immunol. 2009 Apr; 123(4):883-888. 19232704
19. Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow’s milk allergy. J Allergy Clin Immunol. 2007 Nov; 120(5):1172–1177. 17935766
20. Saarinen KM, Pelkonen AS, Mäkelä MJ, Savilahti E. Clinical course and prognosis of cow's milk allergy are dependent on milk-specific IgE status. J Allergy Clin Immunol. 2005 Oct; 116(4):869-875. 16210063
21. Sicherer SH, Sampson HA. Cow's milk protein-specific IgE concentrations in two age groups of milk-allergic children and in children achieving clinical tolerance. Clin Exp Allergy. 1999 Apr; 29(4):507-512. 10202365
22. Fiocchi A, Schünemann HJ, Brozek J, et al. Diagnosis and rationale for action against cow's milk allergy (DRACMA): A summary report. J Allergy Clin Immunol. 2010 Dec; 126(6):1119-1128. 21134569
23. Martorell A, García Ara MC, Plaza AM, et al. The predictive value of specific immunoglobulin E levels in serum for the outcome of the development of tolerance in cow's milk allergy. Allergol Immunopathol (Madr). 2008 Nov-Dec; 36(6):325-330. 19150031
24. Shek L P, Soderstrom L, Ahlstedt S, Beyer K, Sampson HA. Determination of food specific IgE levels over time can predict the development of tolerance in cow’s milk and hen’s egg allergy. J Allergy Clin Immunol. 2004 Aug; 114(2): 387–391. 15316521
25. Sicherer SH, Sampson HA. Cow’s milk protein-specific IgE concentrations in two age groups of milk-allergic children and in children achieving clinical tolerance. Clin Exp Allergy. 1999 Apr; 29(4): 507–512. 10202365
26. D’Urbano LE, Pellegrino K, Artesani MC, et al. Performance of a component-based allergen-microarray in the diagnosis of cow’s milk and hen’s egg allergy. Clin Exp Allergy. 2010 Oct; 40(10):1561–1570. 20633029
27. Hochwallner H, Schulmeister U, Swoboda I, et al. Visualization of clustered IgE epitopes on alpha-lactalbumin. J Allergy Clin Immunol. 2010 Jun; 125(6):1279-1285. 20466413
28. Ford LS, Bloom KA, Nowak-Wegrzyn AH, Shreffler WG, Masilamani M, Sampson HA. Basophil reactivity, wheal size, and immunoglobulin levels distinguish degrees of cow's milk tolerance. J Allergy Clin Immunol. 2013 Jan; 131(1):180-186. 22819512

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
603927 IgE Milk w/ Component Reflex 7258-7 602444 Class Description N/A
603927 IgE Milk w/ Component Reflex 7258-7 606844 F002-IgE Milk kU/L 7258-7
Reflex Table for F002-IgE Milk
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603848 Panel 603848 602731 F076-IgE Alpha Lactalbumin kU/L 7445-0
Reflex Table for F002-IgE Milk
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603848 Panel 603848 602505 F077-IgE Beta Lactoglobulin kU/L 41397-1
Reflex Table for F002-IgE Milk
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 603848 Panel 603848 602554 F078-IgE Casein kU/L 6062-4

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