Anaphylaxis Induced by a Drug Containing Lysozyme and Papain: Influence of Papain on the IgE Response

Abstract

Background: This paper reports the case of an egg-allergic pediatric patient who, once desensitized to egg following a successful rush oral immunotherapy protocol, could also tolerate Lizipaina®, a drug containing lysozyme (LYS) and papain, which had previously caused him a severe allergic reaction. Because the LYS amount that elicited the anaphylactic reaction (5 mg) was much lower than that tolerated during a double-blind placebo-controlled food challenge (corresponding to approximately 60 mg of LYS), the possibility that the presence of papain could increase the allergenic potential of LYS was investigated. Methods: Lizipaina, LYS and LYS hydrolyzed with papain were analyzed by SDS-PAGE under reducing and nonreducing conditions, and Western blotting of sera from egg-allergic patients was performed in order to detect IgE-binding fragments. Finally, sequence identification of the IgE-reactive bands was carried out by MALDI-TOF/TOF. Results: The SDS-PAGE pattern of LYS treated with papain under nonreducing conditions showed the presence of intact LYS that partially disappeared following reduction with β-mercaptoethanol, releasing IgE-reactive fragments as determined by Western blotting. MALDI-TOF/TOF revealed that papain degraded LYS, giving rise to three IgE-binding fragments: LYS (22-129), LYS (34-96) and LYS (62-128) that likely remained linked through the disulfide bonds present in the LYS molecule. Conclusion: The combined administration of LYS with proteolytic enzymes such as papain may have developed a severe allergic reaction in the patient studied, underlining the importance of considering all the components and their interactions when drugs are to be consumed by allergic persons.

Can food processing produce hypoallergenic egg?

“…It constitutes about 3.4% (w/w) of total egg white protein and is used to inhibit gram‐positive bacteria in various foods (Roldán, Lloret, & Palacios, 2017; Sheng, Wang, Huang, Xu, & Ma, 2016). Lysozyme has four disulfide bonds, which may contribute to its allergenicity (Benedé, Pérez‐Rangel et al., 2014). It is reported to show increased IgE‐binding capacity after in vitro simulated gastric digestion, possibly due to the production of peptides with high IgE affinity (Jiménez‐Saiz, Martos, Carrillo, López‐Fandiño, & Molina, 2011).…”

Egg proteins as allergens and the effects of the food matrix and processing

“…This implies that the allergens need to retain a certain structure during their passage through the gastrointestinal tract, resisting the effects of the low pH of the stomach, proteolytic enzymes, and surfactants, such as phospholipids and bile salts, even if, in some cases, the rapid occurrence of allergic symptoms in sensitized individuals suggests that just pregastric contact or absorption of the allergens in the oral cavity or the oesophagus could induce an allergic reaction. 51,52 Thus, resistance to digestion is regarded as one of the common properties of food allergens, although digestibility is not a consistent predictor of allergenicity. [53][54][55][56][57] Structural characteristics, such as a compact quaternary structure, the existence of disulphide bridges, or the binding of sugars or other ligands, have been associated with a greater stability of the allergens towards digestion and a reduced accessibility of the potential peptide bonds to proteolytic enzymes.…”

“…35 In addition to its valuable biological properties, LYS is also a major allergen in egg white, although its allergenic potential has not been studied in depth and few relevant IgE-binding epitopes have been identified. 52,76 At least 35% of patients with clinically observed hen egg hypersensitivity have IgE against LYS, 124,125 and this high frequency of sensitization poses a risk, not only when egg is consumed, but also when LYS of egg origin is used as an antibacterial additive to prevent the spoilage of cheese, wine, or other foods, 126 or in medicinal products. 52 The LYS structure plays an important role in its immunogenicity.…”

Paper based microfluidic aptasensor for food safety

“…Hen egg is known as one of the most common cause of food allergies both in children and adults. Lysozyme of egg origin is one of the main egg white proteins and being increasingly used in the dairy industry as an antibacterial additive to prevent spoilage of many foodstuffs such as cheese and wine, as well as some medicinal products (Benedé et al, 2014). However, lysozyme is a potential food allergen and accounts for 10-20% of egg allergy which may cause immediate or late adverse reactions such as vomiting, nausea, itching, urticarial and so on (Marseglia et al, 2013).…”