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Allergen Encyclopedia
Table of Contents

Component

k208 Gal d 4

k208 Gal d 4 Scientific Information

Type:

Component

Name; WHO/IUIS:

Gal d 4

Biological function:

Glycosyl Hydrolases

Allergen code:

k208

Source Material:

Egg extract

Other Names :

Gal d IV, a362, k208, lysozyme, E1105

Whole Allergen: Egg
Related Allergens: f233 Gal d 1, f232 Gal d 2, f323 Gal d 3, conalbumin/ ovotransferrin, Gallus domesticus egg

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 4 (also known as lysozyme) is one of the egg white proteins and is considered a major 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%. 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 4, are used to characterize the egg allergy.

Gal d 4, present in egg white, is considered a major allergenic protein molecule responsible for allergic reactions among egg-allergic children. Around 30 – 40 % of egg allergy patients are sensitized to Gal d 4. It constitutes around 3% ­­- 3.4 % of the total protein content in egg white and possesses antibacterial property. Lysozyme is utilized by the food (cheese, wine, etc.) and pharmaceutical (like eye drops) industry as a preservative due to its antibacterial properties. Lysozyme is a heat-labile protein and even susceptible to enzymatic digestion. The process of heating or enzymatic digestion of Gal d 4 has been found to depress its allergenicity. Therefore, allergy towards Gal d 4 occurs when raw forms of the egg are consumed. Allergic reactions related to lysozyme have been reported in cases after consumption of drugs containing lysozyme chloride and among bakery workers. Gal d 4 protein present in egg white exhibit cross-reactivity with Gal d 5 and Gal d 6 proteins present in egg yolk. Hence, sIgE in serum towards Gal d 4 can be regarded as a beneficial tool to investigate and predict egg white allergy.

Epidemiology

Worldwide distributions

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), with the prevalence rate ranging between 1.3-1.6% (2, 3). 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) (4). Gal d 4 (lysozyme)  has been regarded as a major allergenic protein responsible for egg allergy (5, 6), usually when ingested in raw form (7).

An Italy-based study reported 36.9% (17/46) of the egg-allergic children (0.7-15.1 years) possessing reactivity towards Gal d 4 (8). Additionally, a China-based study conducted on 99 allergic individuals reported 44% (44/99) of these patients to possess detectable Gal d 4 sIgE (6).

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) (9). According to a study, Gal d 4 (lysozyme) sIgE sensitization can even manifest allergic reactions towards foods or drugs containing this protein (7). A Finland-based study on 185 egg-sensitized children (1-19 years) reported Gal d 4 sensitization among 23% of the study population (10).

Furthermore, a study involving 83 egg white-sensitized individuals from different countries (Europe, US, and Japan) reported the rate of IgE reactivity towards Gal d  4 to be 58% (48/83) of the study population (11). Besides, egg sensitization among the adult population has been reported in few studies. A US-based cohort study reported the prevalence of egg sensitization in the adult population ranging between 2.1% to 3.9% among 4425 adults (20-60+ years) (12).

Environmental Characteristics

Source and tissue

The International Union of Immunological Societies (IUIS) has listed Gal d 4 (lysozyme) protein as a food allergen from Gallus gallus domesticus (hen’s egg ) (13).

Gal d 4 has been reported to contribute around 3 to 3.4% of the total protein content in egg white (6, 10, 14-16).

Lysozyme, a glycosidase, has been reported to be extensively utilized by food (cheese, wine, etc.) and pharmaceutical (like eye drops) industry as a preservative due to its antibacterial properties (11, 14, 17, 18).

Risk factors

According to studies, lysozyme (Gal d 4) used as an adjuvant during wine processing and pharmaceutical products can manifest adverse impact among individuals allergic to hen’s egg (18, 19).

Clinical Relevance

Disease severity

Egg white allergy has been reported as one of the most predominant IgE-mediated food allergies among infants and children (20). Individuals with suspected egg allergy might experience allergic reactions such as anaphylaxis, gastrointestinal (GI) symptoms, skin reactions, respiratory conditions, and mucous membrane reactions after consumption of egg white (21).

Moreover, a case study reported Gal d 4 mediated immediate allergic reactions (like urticarial outbreak, contact urticaria, asthma, and anaphylactic shock), which manifested post-consumption of drug-containing lysozyme chloride (19). An oral food challenge (OFC) study conducted on four bakery workers (27-54 years) also reported occupational allergic symptoms such as chest tightness, wheezing, dyspnea, and cough preceded by nasal symptoms such as itching, sneezing, and runny nose. All the patients exhibited a positive skin prick test (SPT) towards lysozyme (Gal d 4).

Furthermore, two patients from the study were also found to possess positive sIgE towards Gal d 4 (lysozyme) (22). Additionally, a study has also reported lysozyme to be capable of manifesting occupational asthma (15). 

Cross-reactive molecules

According to a study, Gal d 4 protein present in egg white has been reported to exhibit cross-reactivity with Gal d 5 and Gal d 6 proteins present in egg yolk (6).

Molecular Aspects

Biochemistry

Gal d 4 has been regarded as an enzyme found in egg white that possesses lytic action on the microorganism’s (gram-positive) cell wall (23). Lysozyme has been identified as a glycosidase and a weak allergenic component present in egg white (11, 14, 24, 25). This protein's molecular weight has been reported to be 14.3 kDa (14, 16, 26). This protein is found to be composed of a single-strain chain of 129 amino acids (27) and possesses four disulfide bonds (26). Gal d 4 (lysozyme) has been identified as a heat-labile protein that is even susceptible to enzymatic digestion (14, 16, 25). The process of heating or enzymatic digestion of Gal d 4 has been claimed to be responsible for decreasing its allergenicity (10).

Isoforms, epitopes, antibodies

Gal d 4.0101 has been identified as an isoallergen from Gal d 4 and is listed in the IUIS database (13).

Diagnostic Relevance

Disease Severity

Gal d 4 has been stated as one of the important allergens present in egg white and can aid clinicians to diagnose egg white allergy (28). According to a study, children with lysozyme sIgE exhibited symptoms like vomiting, abdominal pain, nausea, and even anaphylactic reaction after challenge with lysozyme containing cheese (29). Therefore, egg white sIgE testing is used as an aid to diagnose egg allergy and also to monitor the disease development. The sIgE diagnostic values have been reported to be a beneficial tool for physicians in deciding the necessity of egg challenge while estimating its potential risk on the patients’ health (21). Hence, periodic monitoring of the absolute values of egg specific-IgE antibody level combined with a clinical history of egg allergy and physical examination can accurately help diagnose egg allergy and indicate when an egg challenge should be performed in patients (14, 15, 30). 

Exposure

The route of exposure for the Gal d 4 (lysozyme) component found in egg white is through ingestion (31).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr Magnus Borres

 

Last reviewed: July  2021

References
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