Gal d 1
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. Gal d 1, also called ovomucoid, plays a crucial role in the pathogenesis of egg white-mediated allergic reactions. 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 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 1, are used to characterize the egg allergy. Most egg-allergic children can develop tolerance to egg proteins over time.
Gal d 1, a protein present in egg white, is considered a major allergenic protein molecule associated with allergic reactions among children. It is a stable protein (allergenicity remains intact), resistant to both heat and enzymatic digestion. An elevated level of Gal d 1 specific IgE (sIgE) has been reported to be correlated with persistent egg allergy. The level of IgE antibodies against Gal d 1 depends on if the patient is allergic to only raw eggs or to cooked eggs, which is a more serious form of egg allergy. Gal d 1 sIgE testing has been reported to aid in the differential diagnosis of the two forms of egg allergy (cooked vs. raw egg) and prognosis of egg allergy in patients. A lower level of sIgE against Gal d 1 has been reported to indicate a tolerance towards the boiled, cooked, or baked egg products. Hence, Gal d 1 sIgE in serum has been regarded as a beneficial tool for investigating persistent egg allergy and allergy towards heated eggs.
Epidemiology
Worldwide distributions
The egg has been reported as one of the common inducers of food allergy prevalent in industrialized countries. Moreover, egg allergy is found to be one of the most frequent childhood food allergies (IgE-mediated), with the prevalence rate ranging between 1.3-1.6%. In egg, egg white is regarded as the primary source of allergens and comprises ovomucoid (Gal d 1), ovalbumin (Gal d 2), ovotransferrin (Gal d 3), and lysozyme (Gal d 4). Gal d 1 (ovomucoid) is considered a major allergenic protein molecule, usually found to be associated with allergic reactions among children. An Italy-based study reported 43.5% (20/46) of the egg-allergic children (0.7-15.1 years) possessing reactivity towards Gal d 1.
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), and among them, 0.8% was sensitized to Gal d 1. Another birth cohort study in Japan found 0.8% of the children (at 9 years) to be sensitized towards Gal d 1. Additionally, a Finland-based study on 185 egg-sensitized children (1-18 years; suspected egg allergy) reported Gal d 1 sensitization prevalence rate among 78% of the study population. An Australia-based study also studied Gal d 1 sensitization prevalence rate and including 297 egg-allergic and 97 egg sensitized but egg tolerant infants (11-20-months old). They reported Gal d 1 sensitization among 67.9% of the egg allergic infants and 32.1% of the egg sensitized but egg tolerant infants.
Clinical Relevance
Disease severity
Egg white allergy has been reported as one of the most predominant IgE-mediated food allergies in infants and children. Individuals with suspected egg allergy might experience allergic reactions such as anaphylaxis, gastrointestinal (GI) reactions, skin reactions, respiratory reactions, and mucous membrane reactions after consumption of egg white.
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. As per a study, ovomucoid (a dominant protein) plays a crucial role in the pathogenesis of egg white-mediated allergic reactions. The study found 94.1% (16/17) patients had responded positively towards heated egg white but negatively to heated and ovomucoid-depleted egg white preparation. According to an oral food challenge (OFC) study, 95% (20/21) of Gal d 1-positive egg-allergic children reacted to raw egg, while 94% (44/47) of Gal d 1 negative children were tolerant to boiled egg.
A study involving 226 egg-allergic children (<6 years) reported the highest tolerance development (73%; 164/226) at 6 years of age. The egg-allergy-related conditions like AD, bronchial asthma, and anaphylaxis were evidently more frequent in patients with prolonged egg allergy. Moreover, infants with prolonged egg allergy had been found to have higher Gal d 1 (ovomucoid)-sIgE level in comparison to other infants without prolonged egg allergy. Additionally, the Gal d 1 sIgE level could also help differentiate egg-allergic children at risk for developing anaphylactic reactions towards egg.
Cross-reactive molecules
A study reported cross-reactivity of the Gal d 1 (ovomucoid) found in hen’s egg white with egg white proteins from turkey, duck, goose, and seagull.
Diagnostics
Disease Severity
Egg IgE has been claimed to be a predictor of egg allergy outcome and can be beneficial to counsel patients on prognosis. According to a case report study conducted by Philippe A. Eigenmann, two patients with negative follow-up food challenges to cooked eggs had subsequently developed anaphylactic reactions to raw eggs. This case report brought attention to the two different forms of egg allergy, cooked vs. raw egg allergy. Specific IgE testing to ovomucoid has been reported as an aid in the differential diagnosis of the two forms of egg allergy and prognosis of egg allergy in patients. The varying level of IgE antibodies against Gal d 1 (ovomucoid) depends on the form of the egg (raw, or cooked, or baked) consumed. A lower level of sIgE against Gal d 1 has been reported to indicate a tolerance towards the boiled, or cooked eggs, or baked egg products. As per a Japanese study, the positive decision and negative decision points for specific IgE to ovomucoid were found to be 10.8kU(A)/L and 1.2 kU(A)/L, respectively. These decision points have been found to be beneficial in guiding physicians to further decide the necessity of food challenges but depend on the clinical characteristics of the studied population. Therefore, the measurement of ovomucoid-sIgE can guide to clinically distinguish between reactivity towards heated and raw egg white. Thus, periodic monitoring of the absolute values of sIgE antibody level towards ovomucoid and clinical history of egg allergy may help clinicians decide the further necessity of OFC test.
Persistent egg-allergic children have been found to possess significantly elevated IgE levels (against native and linearized epitopes of ovomucoid) compared to the transient allergic children. Therefore, Gal d 1 (ovomucoid) sIgE in serum has been regarded as a beneficial screening tool for persistent egg allergy and allergy towards heated eggs (even if the patients show a reaction to raw eggs).
Furthermore, a study reported Gal d 1 (ovomucoid) to be a better component in distinguishing egg allergy from asymptomatic sensitization.
Exposure
The route of exposure for the Gal d 1 (ovomucoid) component found in egg white is through ingestion.
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