title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM, University Hospital, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Benedé
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Pérez-Rangel
authors.forename: Daniel
authors.initials: D
authors.lastname: Lozano-Ojalvo
authors.forename: Elena
authors.initials: E
authors.lastname: Molina
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Ibañez
authors.forename: Rosina
authors.initials: R
authors.lastname: López-Fandiño
authors.forename: Iván
authors.initials: I
authors.lastname: López-Expósito
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000707:Anaphylaxis / Q000276:immunology*; D004342:Drug Hypersensitivity / Q000276:immunology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000276:immunology*; D021181:Egg Hypersensitivity / Q000276:immunology / Q000628:therapy; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000276:immunology*; D010206:Papain / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology
chemical_list: D010446:Peptide Fragments; D007073:Immunoglobulin E; D009113:Muramidase; D010206:Papain