Cow’s milk and Hen’s Eggs

Learning objectives

After this chapter, participants will be able to:

• describe cross-reactivities related to cow’s milk and hen’s eggs components
• explain how component-resolved diagnostics can be applied in the diagnosis of cow’s milk and hen’s egg allergies.

Cow’s milk and hen’s egg allergies

• Cow’s milk and hen’s egg (hereafter referred to as milk and egg, respectively) are staple ingredients in cuisines worldwide.
• Both milk and egg can induce allergy in individuals, particularly in infants and young children.^1,2 However, resolution of these allergies may occur over time.^3,4
• In children under the age of two:
  • The incidence of milk allergy was highest in the UK (1.26%) and lowest in Greece (0.00%).⁵
  • The incidence of egg allergy was also highest in the UK (~2%) and lowest in Greece (0.11%).⁶
• Exposure to aerosolised egg particles can also lead to occupational egg allergies in adults – this has been reported in bakera⁷ and individuals working in embryological research facilities.⁸
• Exposure to heat such as baking may reduce the allergenicity of milk and egg, making it tolerable in patients with clinically relevant allergies.⁹

Allergen components in egg and milk¹⁰

• Several allergen components have been identified in egg and milk:

Key allergen components in eggs

• Although Gal d 2 is the most abundant protein in egg whites,⁹ Gal d 1 is considered to be the dominant major allergen.¹³
• Sensitisation to egg lysozyme (Gal d 4), often used as a bacteriolytic preservative in food, has been shown to be of potential clinical relevance.¹⁴
• Egg allergies in adulthood can be due to the manifestation of “bird-egg syndrome, a cross-reactivity caused by shared IgE epitopes of budgerigar feathers, hen feathers and egg yolk alpha-livetin.¹⁵

Key allergen components in milk

*less stable than casein proteins
Table adapted from Refs ^10,16

• The αS1-caseins and αS2-caseins from cow, goat and sheep share high amino acid sequence identities (87–98%) and cross-reactivities in the laboratory.¹⁷ In patients with cow’s milk allergies, over 90% were also positive for goat’s milk allergy.¹⁸
• Although rare, individuals with persistent milk allergies can also react to serum albumin proteins in different mammalian meats. For example, bovine serum albumin (Bos d 6) has been shown to be involved in the co-sensitisation to milk and beef.¹⁹

Component-resolved diagnosis (CRD) in egg allergies

• Current routine diagnostics for egg allergies use specific IgE blood tests or skin-prick testing.¹⁰ However, the utility of CRD in elucidating the specific allergens that are eliciting a reaction has been investigated:
  • CRD using Gal d 1 (ovomucoid) has been shown to predict clinically relevant egg allergy.^20,21
  • CRD for Gal d 4 may be a useful tool to detect specific IgE against lysozyme in egg-allergic patients.^14,16
  • Multiplex CRD for Gal d 1 in children residing in Italy showed that those who were negative for Gal d 1 had a high frequency of tolerance to boiled egg, whereas Gal d 1 – positive children showed a high frequency of raw egg allergy.²²

CRD can be used to support allergy diagnosis; a definitive conclusion on clinical relevance should be drawn from an indicative medical history, diagnostic tests and, if necessary, an open or double-blind, placebo-controlled challenge with cooked or raw egg forms.^8,16

CRD may be useful in distinguishing patients with raw egg or cooked egg allergies.

CRD in milk allergies

• Current routine testing is via specific IgE blood tests and skin prick tests using complete milk extracts.10 However, the utility of CRD in elucidating the specific allergens that are eliciting a reaction has been investigated:
  • One study in Northern China showed that specific IgE against Bos d 12 had the highest diagnostic performance for milk allergies, whilst specific IgE against Bos d 4 showed the weakest performance. Milk allergy diagnosis improved in accuracy using combinations of milk allergen components, for example Bos d 5 + Bos d 12.²³
  • High IgE levels to three milk components (α-lactalbumin, Bos d 4; β-lactoglobulin, Bos d 5 and casein, Bos d 8) in patients before oral immunotherapy were associated with a less successful outcome of therapy. Therefore, CRD may be useful in the selection of patients with cow’s milk allergy for immunotherapy.²⁴
  • CRD measuring casein (Bos d 8) – specific IgE provided a significantly greater accuracy for predicting baked milk reactivity compared to the β-lactoglobulin component and the more traditional diagnostic tests measuring specific IgE to cow’s milk extract.²⁵

CRD may be useful in predicting which patients are more likely either to respond to oral immunotherapy or to tolerate baked milk goods.

Can component-resolved diagnostics replace oral food challenges in milk and egg allergy?

Summary

• CRD can be used to distinguish primary sensitisations from cross-reactions in patients with cow’s milk and hen’s egg allergy, directing appropriate management.
• CRD may be useful in determining whether patients are able to tolerate baked or cooked milk or egg.
• CRD may be useful in predicting whether patients might respond to oral immunotherapy.

References

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2. Savage JH et al. J Allergy Clin Immunol. 2007;120(6):1413–7.
3. Sicherer SH et al. J Allergy Clin Immunol. 2014;133(2):492–9.
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16. Kleine-Tebbe J, Jakob T. (Editors). Molecular Allergy Diagnostics. 2015. Cham: Springer International Publishing.
17. Walter SP et al. Allergy. 1997;52(3):293–8.
18. Bellioni-Businco B et al. J Allergy Clin Immunol. 1999;103(6):1191–4.
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20. D’Urbano LE et al. Clinical & Experimental Allergy. 2010;40(10):1561–70.
21. Haneda Y et al. J Allergy Clin Immunol. 2012;129(6):1681–2.
22. Alessandri C et al. Clinical & Experimental Allergy. 2012;42(3):441–50.
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24. Kuitunen M et al. Allergy. 2015;70(8):955–62.
25. Caubet J-C et al. J Allergy Clin Immunol. 2013;131(1):222–4.