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Whole Allergen

f75 Egg yolk

f75 Egg yolk Scientific Information

Type:

Whole Allergen

Display Name:

Egg yolk

Route of Exposure:

Ingestion

Family:

Phasianidae

Species:

Gallus gallus

Latin Name:

Gallus spp.

Other Names:

Egg yolk

Summary

Hen’s egg (Gallus gallus domesticus) is a protein-rich food source and is usually consumed as raw, cooked, or processed. Egg yolk is rich in proteins and some of them are regarded as allergenic. The egg yolk has two clinically important allergens, which are Gal d 5 (alpha-livetin/chicken serum albumin) and Gal d 6 or YGP42 (a lipoprotein).The egg yolk proteins are found to be less allergenic compared to the proteins derived from egg white. Most egg allergy studies have therefore used specific IgE test to egg white and not to egg yolk when documenting egg sensitization. The egg has been considered one of the most common food allergy sources, particularly in infants and children. Around 0.5 – 2.5 % of young children within a normal population have been found to be allergic to eggs. However, the prevalence of egg allergy in adults is less than 0.25 %. Egg sensitization, having IgE antibodies to egg, is a prerequisite for egg allergy. Egg sensitization is more prevalent than egg allergy, and the prevalence rate has been reported to be up to 6 % depending on age. Most egg-allergic children can develop tolerance to egg proteins over time. A patient's highest recorded egg sIgE is significantly related to the persistence of egg allergy. A higher egg sIgE value denotes a more extended period to develop tolerance. Egg allergic patients might experience symptoms or reactions after consumption of egg that include gastrointestinal reactions (vomiting, abdominal pain), skin symptoms (localized or generalized urticaria, erythema, facial angioedema), and respiratory conditions (asthma and/or rhinitis). Therefore, egg allergic individuals are usually recommended to strictly avoid egg products. Moreover, egg allergic children are often falsely denied influenza or MMR vaccination as the vaccine might contain a small amount of egg protein. However, several studies and guidelines have claimed these vaccines to be safe for children with egg allergies.

An oral food challenge (OFC) is usually considered the gold standard for diagnosing egg allergy but challenges with egg yolk are very rare. Heated egg yolk OFCs has been found to rarely provoke severe symptoms and may be recommended for improving the quality of life (QOL) of hen’s egg allergic children. Egg sIgE testing can aid in diagnosing egg allergy and is predictive of allergy outcome; therefore, it should be utilized in counseling patients on prognosis. Furthermore, egg allergy and egg sensitization has been found to elevate the risk of developing sensitization to aeroallergens (such as grass pollens, house dust mites, cats, and dogs).

Bird-egg syndrome, a type 1 hypersensitivity-mediated respiratory disorder including asthma and/or rhinitis, has been reported to be associated with sensitization to Gal d 5. This condition usually manifests as primary sensitization towards airborne bird allergens (like bird blood serum, feathers, droppings, and dander) followed by secondary sensitization or cross-sensitization with Gal d 5 (egg yolk) post-consumption. Therefore, Gal d 5 sIgE testing has been claimed to be beneficial in diagnosing bird-egg syndrome.

Allergen

Nature

Egg (Gallus gallus) is a food product with substantial nutritional content, suitable and popular among individuals of all ages (children, adults, elderly). Both egg white and egg yolk are the edible parts of egg and are rich in proteins. The egg is reported to contain both macro and micronutrients required for embryonic development until hatching (1).

Egg yolk is a rich source of lipids, vitamins, and minerals. The proteins present in egg yolk mainly comprise of phosvitins, livetins, low-density lipoproteins (LDL), high-density lipoproteins (HDL), vitellenin, and apoprotein B (1, 2). Allergens present in the egg are known to be there in both egg yolk and egg white (3); however, the egg yolk proteins are found to be less allergenic compared to the proteins derived from egg white (4). The egg yolk has been reported to possess two clinically important allergens, which are Gal d 5 (alpha-livetin/chicken serum albumin), a heat-labile protein, and Gal d 6 or YGP42 (a lipoprotein), a heat-resistant protein (3, 5, 6). Moreover, Gal d 5 has been claimed as a major allergen present in egg yolk (6, 7).

Globally, eggs have been extensively utilized in food products like bread, egg noodles, pancakes, waffles, cakes, French toast, tea-boiled egg, and others (8). Egg yolk is  majorly used in products like salad dressing, sauces, confectionery, creams, noodles, baking goods, and mayonnaise (9).

Habitat

Hen’s eggs are regarded as fresh up to 28 days post laying. Room temperature or preferably refrigeration is considered ideal for the storage of shelled eggs. Variation in storage condition and duration for eggs can induce physiochemical changes and further protein denaturation. These changes are manifested due to the exchange of water between egg white and yolk, loss of carbon dioxide and water through the pores in eggshells, further resulting in increased air cell volume (1).

Taxonomy

Gallus domesticus (Hen’s egg) belongs to the family Phasianidae (chicken) (10).

Taxonomic tree of Hen’s Egg (10)
Domain Eukaryota
Kingdom Animalia
Phylum Chordata
Subphylum Vertebtata
Class Aves
Order Galliformes
Family Phasianidae
Subfamily Phasianinae
Genus Gallus
Species Gallus gallus
Sub-species Gallus gallus domesticus
Taxonomic tree of Hen’s Egg (10)

Tissue

The average protein concentration of a whole egg is found to be 12.5g/100g of a raw fresh egg, while the average protein concentration of egg white (including vitelline membrane) might be 10.9g/100g of a raw fresh egg. Egg white and egg yolk are separated by the vitelline membrane that prevents seepage of egg yolk content into the egg white. The vitelline membrane’s strength has been reported to reduce with prolonged storage, resulting in a flatter yolk with a larger diameter.These modifications further result in an exchange of components (glucose, carbohydrates, vitamins, proteins, and other trace elements) between the egg white and yolk (1).

Egg yolk has been reported to be primarily comprised of carbohydrates (1%), lipids (31 to 35%), proteins (15 to 17%), and water (50%). Low-density lipoproteins (17%), phosvitin (8%), livetins (38%), and lipovitellins (36%) are the proteins present in egg yolk. The yellow color of the yolk has been found to be imparted by the presence of carotenoids (1%) (11).

During the cooking process, egg proteins are claimed to undergo significant conformational modifications (based on heating temperature and cooking time), leading to protein denaturation. This process of protein denaturation may lead to the inactivation of antinutritional factors like antiprotease from egg-white and other highly resistant proteins in eggs (1).

Epidemiology

Worldwide distribution

The egg has been reported as one of the common inducers of food allergy prevalent in industrialized countries (12). According to a study, around 0.5-2.5% of young children have been observed to be affected with egg allergy (13, 14). An Italy-based study involving 104 suspected egg-allergic patients (0.7-15.1 years) reported 4.3% (2/46) of patients to exhibit allergenicity towards Gal d 5 (egg yolk) (15). Another study conducted in Japan found 9.1% (18/197) of the egg-allergic children (12.1-23.8 months) to react positively with the heated egg yolk slightly contaminated with egg white (4).  Furthermore, a China-based study involving 56 egg-allergic children (0.5-8 years) also detected Gal d 5 specific IgE (sIgE) among 23.2% of the study population (2). Moreover, adults have been found to exhibit more reactivity towards the proteins found in egg yolk (Gal d 5 and Gal d 6) (16). A US-based cohort study detected the prevalence of egg allergy to be approximately <0.25% (from graphical representation) in 4425 adults (20-60+ years) (17).

Sensitization to the egg means that IgE antibodies are produced towards the egg and is a prerequisite for an IgE-mediated egg allergy. Egg sensitization is more prevalent than egg allergy, and IgE antibodies have been detected already in very young age groups. Tedner et al. found in a Nordic population-based birth-cohort study the prevalence of egg sensitization among 3-month old infants to be 3.7% (41/1102) (18). Another cohort study in Sweden on 2336 children (4 years) claimed the prevalence of egg sensitization as 5% (112/2336) (19). Moreover, a German-based cohort study confirmed the highest sensitization towards hen’s egg (around 6%) in infants at 1 year of age (20). Besides, egg sensitization among the adult population has also been reported in few studies. A European cohort study found an overall prevalence of egg sensitization to be 0.4% among the adult (20-39 years) population (21). Furthermore, a US-based cohort study also reported the prevalence of egg sensitization ranging between 2.1% to 3.9% among 4425 adults (20-60+ years) (17).

Natural History of Egg Allergy

Food allergy during childhood could be a transitory condition, although in some cases, it is a persistent one. Hen’s egg has been reported to be one of the frequent food allergens affecting children during the first ten years of life  (22). Egg allergy has been claimed to get resolved naturally with aging (2-6 years) (6, 23). A study conducted on 881 egg-allergic patients (10-23 months old) reported the development of tolerance towards eggs by the age of 4 years in 4% cases and by 16 years in 68% cases. A gradual decline in egg sIgE level was evident with aging among patients with persistent egg allergy; in contrast, a sharp decline in egg sIgE was found in egg-allergy resolved (tolerant) patients from this study (24). A study conducted on 226 egg-allergic children (<6 years) reported tolerance development in 30% (66/226) of children by the age of 3 years, while in 73% (164/226) of children by 6 years (25). 

According to a study, egg allergic children might possess sensitization towards egg yolk Differentiation of egg allergy, egg yolk resistance, and egg yolk reactivity (with slight egg white contamination) might be utilized to forecast the natural course of egg allergy during the early stages of life (3). 

Risk factors

Egg allergy is associated with atopic dermatitis (AD), asthma, rhinitis, and other food allergies (such as peanut) (14). Clinical allergy towards eggs has been found to be associated with risk factors like male gender, young age, ethnicity/race (Liu, Jaramillo et al. 2010), and family history (26). Moreover, the presence of sIgE towards all four egg allergens (Gal d 1, 2, 3, or 5) has been reported to elevate the risk of developing persistent raw egg allergy (27). Additionally, heated egg yolk-reactive patients have been found to exhibit a higher probability of developing persistent egg allergy (4). Also, bird-egg syndrome (IgE mediated hypersensitivity towards egg yolk) has been reported to be prevalent among the adult population, predominantly in the female gender (28).

Children with egg allergy are often denied influenza vaccination because the vaccine contains a small amount of egg protein. However, recent studies have demonstrated that children with even severe egg allergy can safely receive the vaccine. Therefore, based on this outcome, the current guidelines recommend routine immunization (influenza vaccination) of such egg-allergic patients without undergoing any testing or special considerations  (29). Moreover, as per the recommendations of vaccination-specific guidelines, the influenza vaccine can be received under usual clinical settings (30). A study conducted on egg-allergic patients immunized with live attenuated influenza vaccine reported no systemic reactions (allergic) or anaphylaxis among these patients post-immunization (31).

National Advisory Committee on Immunization (NACI) has deemed patients with egg allergy suitable for receiving MMR vaccination. According to this guideline, the immunization may be administered without prior testing but under proper guidance and adequate facility (in case of food-induced symptoms like anaphylaxis) (32).

Pediatric issues

A significant correlation exists between sensitization towards outdoor/indoor aeroallergens (like grass pollens, house dust mites, cat, dog) and egg allergy during infancy (33, 34). Additionally, the coexistence of egg allergy and eczema at infancy has also been reported as a predictive indicator of aeroallergen sensitization and respiratory allergies among children (4 years) (33).

Environmental Characteristics

Worldwide distribution

Hen’s egg is consumed globally in various forms like raw, semi-cooked (poached or soft-boiled eggs) (1), completely cooked (hard-boiled, scrambled, baked, or fried) (35) or as an additive in products like bread, waffles, cakes and others (8). Additionally, eggs are also utilized in the cosmetic, pharmaceutical (especially vaccine preparation), and beverage refining (wine and beer) industry (35).

Route of Exposure

Main

The route of exposure is through ingestion (consumption) of egg yolk or egg (36).

Clinical Relevance

Egg yolk allergic patients might experience symptoms or reactions after consumption of egg yolk or egg based products that include gastrointestinal reactions (vomiting, abdominal pain), skin symptoms (localized or generalized urticaria, erythema, facial angioedema), and respiratory conditions (asthma and/or rhinitis) (24, 36-38).

Gastrointestinal (GI) symptoms

GI symptoms are mostly seen as immediate hypersensitivity reactions in egg-allergic individuals (34). According to a study, 21% (78/881) of the patients showed GI reactions (like abdominal pain, bloody stool, diarrhea, vomiting) as initial symptoms of egg allergy (24). 

Skin reactions and Atopic dermatitis

Skin reactions like urticaria or angioedema are reported as IgE-mediated common allergic reactions prevalent in children (within minutes to a few hours) post-consumption of eggs (34). According to a study on 8 patients with respiratory symptoms to bird feathers, consumption of undercooked egg yolk (fried) and mayonnaise immediately resulted in burning and itchy sensation in the mouth, followed by swelling of lips/oral mucosa, and facial angioedema (rarely) (38). Moreover, a study conducted on 122 patients with AD reported a positive skin prick test (SPT) towards egg yolk in 7.4% of the study population (39).

Asthma and other respiratory symptoms

Gal d 5 sensitized patients are found to frequently develop respiratory symptoms like asthma and rhinitis following consumption of egg (37). A study conducted on 452 asthmatic and 2062 allergic rhinitis patients reported a positive SPT towards egg yolk in 6.4% and 5.9% of the study population, respectively (39). 

Bird-egg syndrome/allergy

Bird-egg syndrome, a type 1 hypersensitivity-mediated respiratory disorder including asthma and/or rhinitis, has been reported to be associated with sensitization to Gal d 5. This condition usually manifests as primary sensitization towards airborne bird allergens (like bird blood serum, feathers, droppings, and dander) followed by secondary sensitization or cross-sensitization with Gal d 5 (egg yolk) post-consumption (6, 7, 37, 40). Therefore, Gal d 5 sIgE testing has been claimed to be beneficial in diagnosing bird-egg syndrome (6, 7). A study was conducted on 8 patients with respiratory symptoms (rhino-conjunctivitis and asthma) to bird feathers and egg allergy symptoms to egg yolk. All the patients were reported to demonstrate a positive SPT and sIgE-reactivity towards Gal d 5 (serum albumin) (38).

Other diseases

Egg allergen can cause non-IgE mediated allergic conditions like eosinophilic esophagitis and eosinophilic gastroenteritis (41). In a case series of 23 adult patients with eosinophilic esophagitis, 17% (4/23) of patients were sensitized to egg yolk (42).

Diagnostics Sensitization

Challenge tests      

Oral food challenge (OFC) is considered the gold standard for diagnosing egg allergy. However, this mode of diagnosis is often regarded as time extensive, resource-consuming, and potentially risky (15, 43).

However, OFC studies, specific for heated egg yolk, are rare. An OFC for heated egg yolk was conducted by Yanagida et al. to find whether hen’s egg-allergic children can consume heated egg yolk. The study reported that the majority of the egg-allergic children could safely consume heated egg yolk. Moreover, heated egg yolk OFCs were found to provoke severe symptoms rarely and hence can be suggested to improve the quality of life (QOL) of the hen’s egg-allergic children (44).

In-vitro diagnostics

Egg sIgE testing is used as an aid to diagnose egg allergy and monitor the disease development. The sIgE diagnostic values have been reported to be beneficial for physicians in deciding the necessity of an egg challenge while estimating its potential risk on the patients’ health. Additionally, an age-specific correlation exists between egg sIgE levels and the outcome of oral food challenge (OFC); younger children usually exhibit reactivity to even at low egg sIgE levels in contrast to the older children (45). Therefore, periodic monitoring of the absolute values of egg sIgE antibody level combined with the clinical history of egg allergy may be beneficial for accurate diagnosis of egg allergy (46).

Prevention and Therapy

Prevention strategies 

Complete avoidance of egg (yolk) and egg-based products from the diet is considered the possible treatment option for egg allergy (7, 36, 47);  however, this could be challenging as hen’s egg being a common ingredient of many foods, chances of accidental intake of egg or egg-based products are usually quite high (6, 47). Moreover, it is almost impossible to fully separate the egg yolk from the egg white without the slightest allergen contamination (28).

Patients allergic to heat-labile egg protein (like ovalbumin and serum albumin or Gal d 5) might be tolerant towards cooked, boiled, or fried form of egg white and yolk (36). Hence, differential avoidance is typically recommended for egg-allergic patients based on their reactivity towards raw or cooked eggs.  Moreover, reactivity towards raw or slightly cooked eggs has been found to be more prevalent compared to extensively processed egg-based food (48).

Furthermore, the early introduction of eggs into the diet has been found to be potentially beneficial in preventing egg allergy (12). In a study conducted on 231 infants allergic to egg, early introduction of egg (4-6 months age) was found to be correlated with a reduced risk of egg allergy. In contrast, late introduction of an egg-based diet (at 10 months) might increase the risk of developing egg allergy (49).

Allergen immunotherapy

Patients hypersensitive towards cooked egg yolk (boiled) might experience challenges in developing egg tolerance. These patients may be advised to undertake oral immunotherapy (OIT) (50). A study was conducted on 30 egg-allergic children (≥4 years) to estimate the efficacy of OIT-egg desensitization and evaluate the maintenance of tolerance. All the patients (n=16) attained desensitization towards egg after 4 months of therapy, while 31% were reported to retain tolerance towards egg even after 3 months of avoiding egg consumption (51).

Molecular Aspects

Allergenic molecules

The allergenic proteins from hen’s egg yolk that have been identified in the IUIS database are listed below in the table (52).

Allergen Biochemical Name  Molecular Weight  Allergenicity 
Gal d 5 Serum albumin 69 kDa

Gal d 5 (serum albumin) is highly prevalent in egg yolk, and a similar type of serum albumin is also found in bird tissues (like muscle tissue). Therefore, individuals sensitized towards serum albumin in hen’s egg may also exhibit poultry meat allergy due to cross-reactivity (53, 54).

According to an OFC study, 4.3% (2/46) of the patients (0.7-15.1 years) exhibited sIgE reactivity towards Gal d 5 (15)
Gal d 6 YGP42 35 kDa Gal d 6 is a thermo-stable, pepsin-digestible protein found in egg yolk. 18% (5/27) of sera from 27 EA patients (2-74 years) was found to show sIgE binding towards Gal d 6 (55)
Allergen Biochemical Name  Molecular Weight  Allergenicity 

sIgE: specific Immunoglobulin E, kDa: kilodaltons, EA: Egg Allergy, OFC: Oral food challenge.

Other additional allergenic components found in egg yolk include phosvitin (transferase protein, 35 kDa), apovitellenins I (very low-density lipoprotein, 9.5 kDa), apovitellenins VI (orapoprotein B, 170 kDa), and yolk glycoprotein 42 (6, 56). 

Biomarkers of severity

Gal d 5 has been reported as a biomarker to detect sensitization towards egg yolk (16).

Cross-reactivity

Hen’s egg yolk proteins (Gal d 5 and Gal d 6) have been found to exhibit cross-reactivity with protein present in egg white (Gal d 1) (3).

Gal d 5 has been reported to be cross-reactive with the aeroallergens of birds (such as bird blood serum, feathers, droppings, and dander) (6, 7, 37, 40). A study has revealed cross-reactivity between egg yolk allergen (Gal d 5) and budgerigar feather containing albumin (53). 

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr Magnus Borres

 

Last reviewed: July  2021

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