Allergen Profile, Milk, IgE With Component Reflexes*

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Turnaround Time: 3-5 days
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Test Type: 1mL Serum


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.

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.

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

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. PubMed 24090398

2. Chokshi NY, Sicherer SH. Interpreting IgE sensitization tests in food allergy. Expert Rev Clin Immunol. 2015:1-15. PubMed 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. PubMed 24483212

4. Sastre J. Molecular diagnosis in allergy. Clin Exp Allergy. 2010 Oct; 40(1):1442-1460. PubMed 20682003

5. Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014 Feb; 133(2):291-307. PubMed 24388012

6. Tsabouri S, Douros K, Priftis KN. Cow's milk allergenicity. Endocr Metab Immune Disord Drug Targets. 2014 Mar; 14(1):16-26. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 18620743

11. Wal JM. Bovine milk allergenicity. Ann Allergy Asthma Immunol. 2004 Nov; 93(5 Suppl 3):S2-11. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 17935766

20. Saarinen KM, Pelkon

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Collection Instructions:

Red-top tube or gel-barrier tube.

Room Temperature.