Gal d 3, conalbumin/ ovotransferrin, Gallus domesticus egg
Summary
Gal d 3, a major allergen of hen’s egg white (Gallus domesticus), belongs to the transferrin family, involved in iron homeostasis and antimicrobial defense. Gal d 3 is sensitive to thermal and physico-chemical processing.
Epidemiology
Worldwide distribution
Hen’s egg is a staple human food. It is also a common cause of allergy, predominantly in pediatric populations and following egg white ingestion [1]. In Europe, data collected from 2005 through 2009 as part of the EuroPrevall study found self-reported allergy to hen’s egg in 9.9% of pediatric subjects (second only to cow’s milk), IgE sensitization to hen’s egg in approximately 5%, and 1% or lower when considering an association of evocative symptoms and IgE sensitization, corresponding to probable allergy to hen’s egg [2]. The same study placed self-reported allergy to hen’s egg at the 4th place of most prevalent food allergy in European adults, however, IgE sensitization was detected in only 0.9%, and probable allergy to hen’s egg in 0.3% or less [3, 4].
Gal d 3 sensitization occurs in a majority of patients allergic to hen’s egg, up to 69% using affinity-purified Gal d 3 [5].
Clinical Relevance
In hen’s egg allergic patients, sensitization to Gal d 3, an allergen sensitive to thermal and chemical processing, may be associated with symptoms induced by raw or incompletely cooked egg white, or even remain asymptomatic. However, egg allergic subjects are usually sensitized to multiple egg allergens, therefore clinical expression in Gal d 3-sensitized subjects may vary accordingly [1, 7, 8].
Disease severity and prediction
Gal d 3 sensitization usually coexists with sensitization to other allergens from hen’s egg white, explaining the lack of a statistically significant association with increased or decreased severity or persistence of this allergy [1, 8, 9]. Polysensitization to hen’s egg allergens, defined as detectable IgE to Gal d 1, Gal d 2, Gal d 3 and Gal d 4 was significantly more prevalent at baseline in children who did not achieve tolerance after 8 months of oral immunotherapy with raw egg [10]. These children also displayed significantly higher baseline levels of IgE to Gal d 3 [10].
Cross-reactive molecules
Given the frequent sensitization rate and the presence of numerous homologs, oral food challenges help define the spectrum of hen’s egg allergy and of its clinical cross-reactivity [1, 11]. In a Japanese cohort of hen’s egg allergic children, skin reactivity to both hen’s egg and quail’s egg (Coturnix japonica, a close relative of Gallus domestica belonging to Galliformes) found in 92% of patients was most often devoid of clinical relevance as assessed by a positive oral food challenge in only 45% of the patients [11]. Conversely, allergy to quail’s egg conalbumin with tolerance to hen’s egg Gal d 3 and isolated sensitization to quail’s egg conalbumin has been reported [12].
Diagnostics
Cross-Reactivity
Gal d 3 displays in vitro cross-reactivity with homologs from egg white of other bird species, as well as various avian meat and serum, however, the clinical relevance might need to be assessed using oral food challenges [11].
AIT Prescription
In hen’s egg allergic patients, the distinction between sensitized and allergic, and between raw versus baked egg allergic patients relies primarily on the heat-resistant ovomucoid Gal d 1 [1].
Exposure
The main route of exposure to Gal d 3 is through egg white ingestion, but it may also happen in distinct circumstances, e.g. through inhalation of aerosolized hen’s egg allergens during the cooking process [1].
References
- Matricardi, P.M., et al., EAACI Molecular Allergology User's Guide. Pediatr Allergy Immunol, 2016. 27 Suppl 23: p. 1-250.
- Lyons, S.A., et al., Prevalence of Food Sensitization and Food Allergy in Children Across Europe. J Allergy Clin Immunol Pract, 2020. 8(8): p. 2736-2746 e9.
- Lyons, S.A., et al., Food Allergy in Adults: Substantial Variation in Prevalence and Causative Foods Across Europe. J Allergy Clin Immunol Pract, 2019. 7(6): p. 1920-1928 e11.
- Burney, P.G., et al., The prevalence and distribution of food sensitization in European adults. Allergy, 2014. 69(3): p. 365-71.
- Everberg, H., et al., Affinity purification of egg-white allergens for improved component-resolved diagnostics. Int Arch Allergy Immunol, 2011. 154(1): p. 33-41.
- Rathnapala, E.C.N., D.U. Ahn, and S. Abeyrathne, Functional properties of ovotransferrin from chicken egg white and its derived peptides: a review. Food Sci Biotechnol, 2021: p. 1-12.
- Hoffman, D.R., Immunochemical identification of the allergens in egg white. J Allergy Clin Immunol, 1983. 71(5): p. 481-6.
- Suprun, M., et al., Mapping Sequential IgE-Binding Epitopes on Major and Minor Egg Allergens. Int Arch Allergy Immunol, 2022. 183(3): p. 249-261.
- Gradman, J., et al., Relationship between specific IgE to egg components and natural history of egg allergy in Danish children. Pediatr Allergy Immunol, 2016. 27(8): p. 825-830.
- Palosuo, K., et al., A Randomized, Open-Label Trial of Hen's Egg Oral Immunotherapy: Efficacy and Humoral Immune Responses in 50 Children. J Allergy Clin Immunol Pract, 2021. 9(5): p. 1892-1901 e1.
- Mitomori, M., et al., Clinical cross-reactivity to quail's egg in patients with hen's egg allergy. Pediatr Allergy Immunol, 2022. 33(3): p. e13754.
- Caro Contreras, F.J., et al., Allergy to quail's egg without allergy to chicken's egg. case report. Allergol Immunopathol (Madr), 2008. 36(4): p. 234-7.
- Osborne TM, C.G., The Protein Constituents of Egg White. J Am Chem Soc, 1900. 22(7): p. 422-450.
- Legros, J., et al., The Role of Ovotransferrin in Egg-White Antimicrobial Activity: A Review. Foods, 2021. 10(4).
- IUIS/WHO. IUIS/WHO Gallus domesticus. 2022 2022 May 16]; Available from: http://allergen.org/search.php?allergenname=&allergensource=chicken&TaxSource=&TaxOrder=&foodallerg=all&bioname=.
- BLAST, U. UniProt BLAST for UniProtKB - P02789 (TRFE_CHICK). 2022 2022 May 16]; Available from: https://www.uniprot.org/blast/uniprot/B202205164ABAA9BC7178C81CEBC9459510EDDEA303E6E0W.
- Langeland, T., A clinical and immunological study of allergy to hen's egg white. VI. Occurrence of proteins cross-reacting with allergens in hen's egg white as studied in egg white from turkey, duck, goose, seagull, and in hen egg yolk, and hen and chicken sera and flesh. Allergy, 1983. 38(6): p. 399-412.