f232 Gal d 2

Summary

Hen’s egg (Gallus gallus domesticus) is a protein-rich food source and is usually consumed as raw, cooked, or processed. Egg white is rich in proteins and is regarded as highly allergenic. One of these proteins is Gal d 2, also called ovalbumin, and it is considered a major egg allergen. The egg has been considered one of the most common food allergy sources, particularly in infants and children, with the prevalence rate ranging between 1.3-1.6%. 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. The specific IgE (sIgE) test for egg white is commonly used as a start when investigating a patient with a suspicion of egg allergy. IgE tests for egg components, such as Gal d 2, are used to characterize the egg allergy. Most egg-allergic children can develop tolerance to egg proteins over time.

Gal d 2 is a protein present in egg white, considered a major allergenic protein molecule associated with egg allergic reactions among children. Ovalbumin is a heat-labile protein and even susceptible to enzymatic digestion. The process of heating or enzymatic digestion of Gal d 2 has been found to be responsible for decreasing its allergenicity. Therefore, allergy towards Gal d 2 is generally found to be associated with uncooked (raw) eggs rather than cooked eggs. Therefore, egg-allergic individuals are recommended to avoid an egg-based diet. sIgE production towards Gal d 2 can elevate the risk of persistent allergy to raw eggs and may be considered an important predictor for raw egg allergy. Moreover, a reduction in Gal d 2 sIgE level has been reported in patients who developed tolerance to the heated egg. Furthermore, persistent egg-allergic children have been found to possess significantly elevated levels of sIgE towards Gal d 2 compared to the children who develop tolerance towards egg.

Epidemiology

Worldwide distribution

The egg has been reported as one of the common inducers of food allergy prevalent in industrialized countries (1). Moreover, egg allergy has been found to be one of the most frequent childhood food allergies (IgE-mediated) (2) with the prevalence rate ranging between 1.3-1.6% (3, 4). In egg, egg white is regarded as the primary source of allergen and comprises ovomucoid (Gal d 1), ovalbumin (Gal d 2), ovotransferrin (Gal d 3), and lysozyme (Gal d 4) (5).  

Gal d 2 (ovalbumin) is considered a major allergen and is found to be mostly associated with allergic reactions among children (6, 7). Besides, Gal d 2 has been reported to be a predominant allergen in countries like Taiwan and Spain (8). A Taiwan-based study on 2256 allergic children (0.1-17.6 years) found reactivity towards Gal d 2 in about 30% (676/2256) of the study population (9). An Italy-based study reported 52.1% (24/46) of the egg-allergic children (0.7-15.1 years) possessing reactivity towards Gal d 2 (10). Moreover, in a Chinese study on 56 egg-allergic children (6 months-10 years), specific IgE (sIgE) towards Gal d 2 was found to be exhibited by 62.5% of the patients (2). Additionally, a US-based cohort study also detected the prevalence of egg allergy to be approximately <0.25% (from graphical representation) in 4425 adults (20-60+ years) (11)

Sensitization to egg white components was mostly seen among children between 2-4 years (9). 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) (12). A Finland-based study on 185 egg-sensitized children (1-18 years; suspected egg allergy) reported Gal d 2 sensitivity among 33% of the study population (13). Moreover, a study involving 83 egg white-sensitized individuals from different countries (Europe, US, and Japan) reported the rate of IgE reactivity towards Gal d 2 to be 87% (72/83) of the study population (14). Similarly, a Thai study found Gal d 2 sensitization to be 93.8% in 32 egg-allergic children (7-99 months) (15). Furthermore, an Australia-based study including 297 egg-allergic and 97 egg-sensitized-tolerant infants (11-20-months old) reported Gal d 2 sensitization among 88.6% of the egg-allergic infants and 48.1% of the egg sensitized-tolerant infants (16).

Environmental Characteristics

Source and tissue

The International Union of Immunological Societies (IUIS) has listed Gal d 2 (ovalbumin) protein as a food allergen from Gallus gallus domesticus (hen’s egg) (17).

Egg white comprises around 24 protein fractions (18). Gal d 2 (ovalbumin) has been claimed to be present abundantly in egg white, constituting about 54% of the total egg white protein (5, 8, 13, 14). Gal d 2 belongs to the serpins superfamily, which primarily acts as a storage protein (19). Ovalbumin (Gal d 2) has been reported to undergo conformational modification to a more stable form (s-Ovalbumin) on storage at high temperatures. This s-Ovalbumin is reported to possess depressed IgE binding capability compared to the ovalbumin and is less allergenic (14, 20, 21). This property of ovalbumin indicates the reason behind children being sensitive to raw egg white but tolerant towards heated forms of egg (14).

Risk factors

A study found Gal d 2 sensitization among infants correlated with an elevated risk of developing persistent egg allergy (16).

Moreover, studies also reported Gal d 2 (ovalbumin) sensitized children to be at an increased risk of developing atopic dermatitis (AD) on ingestion of raw or slightly processed egg white (9, 19).

Clinical Relevance

Disease severity

Egg white allergy has been reported as one of the most predominant IgE-mediated food allergies in infants and children (22). Individuals with suspected egg allergy might experience allergic reactions such as anaphylaxis, gastrointestinal (GI) symptoms, skin reactions, and respiratory conditions after consumption of egg white (23).

The tolerance towards hen’s egg has been reported to initiate with tolerance towards heated egg (boiled or cooked) followed by a gradual development of tolerance towards raw egg (24). According to a study on egg-allergic and egg-sensitized-tolerant infants (11-20-months old), Gal d 2 was found to be the most frequent allergen. Also, the majority of the infants sensitized exclusively to Gal d 2 have been found to possess transient egg allergy, and most of these infants (90%) had developed tolerance by 4 years of age (16).

A study conducted on 2256 children (0.1 to 17.6 years) with allergic diseases reported 48.6% (18/37) of the children (with both AD and asthma) exhibited sensitization for Gal d 2 (ovalbumin) (9). Moreover, a food challenge study reported anaphylaxis in 8% (3/38) of the patients allergic to both heated and raw egg white. Two of these children have been identified to exhibit high Gal d 2 (ovalbumin) sIgE level (25). Gal d 2 sIgE level could also help differentiate egg-allergic children at risk for developing anaphylactic reactions towards egg (5).

Cross-reactive molecules

A study reported cross-reactivity between ovalbumin (Gal d 2) found in hen’s egg white and egg white proteins from turkey, duck, goose, and seagull (26). Besides, cross-reactivity between ovalbumin (Gal d 2) present in hen’s egg white and Gal d 5 and apovitellenin I proteins present in hen’s egg-yolk has been reported by studies (27, 28).

Molecular Aspects

Biochemistry

Gal d 2 (ovalbumin) is an immunodominant protein present in egg white (18). It is a phosphorylated glycoprotein (14, 21) with a molecular weight of around 44 kDa (19). The protein comprises 385 amino acids and six cysteine (Cys) residues along with a disulfide bond present between Cys73 and Cys120 (21, 29). The carbohydrate chains of this protein have been reported to possess high levels of mannose sugar, which could be responsible for its allergenicity (20).

Gal d 2 has been reported as a heat-labile protein (22) and even susceptible to enzymatic digestion (13). Moreover, Gal d 2 (ovalbumin) has been found to be marginally digested by pepsin at a pH range of 1.5-2.0 and reported to be enzyme-resistant at a pH of 2.5 and above (30). The process of heating or enzymatic digestion of Gal d 2 has been found to be responsible for decreasing its allergenicity (13). Therefore allergy towards Gal d 2 is generally found to be associated with uncooked eggs rather than cooked eggs (2).

Isoforms, epitopes, antibodies

Gal d 2.0101 has been identified as an isoallergen for Gal d 2 and has been listed in the IUIS database (31).

Diagnostic Relevance

Disease Severity

Egg IgE has been found to be a predictor of allergy outcome and can be beneficial to counsel patients on prognosis (32). According to a case report study conducted by Philippe A. Eigenmann, two patients with negative follow-up for food challenge towards cooked eggs had subsequently developed anaphylactic reaction to raw eggs. This case report brought attention to the two different forms of egg allergy, cooked vs. raw egg allergy (33). Specific IgE production towards Gal d 2 has been reported to elevate the risk of persistent allergy to raw eggs. Therefore, Gal d 2 sIgE testing (periodically) has been reported as one of the best predictors in diagnosing allergy towards raw eggs (16). A reduction in Gal d 2 sIgE level has been reported in patients who developed tolerance to heated egg (22). Moreover, sensitization towards Gal d 2 (devoid of Gal d 1 sIgE) has been found to be beneficial in determining reactions towards raw eggs (13). According to studies, persistent egg-allergic children have been found to possess significantly elevated levels of sIgE towards Gal d 2 (both native and linearized) compared to the children who develop tolerance towards egg (34, 35). Moreover, Gal d 2 sIgE level has been found to be effective in identifying children who are intolerant to raw eggs (36). Thus, periodic monitoring of the absolute values of sIgE antibody level towards ovalbumin (Gal d 2) and clinical history of egg allergy may help clinicians to decide the further necessity of oral food challenge test (24, 34, 37).

Exposure

The route of exposure for the Gal d 2 (ovalbumin) component found in egg white is through ingestion (19).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr Magnus Borres

Last reviewed: July  2021