title: Alpha-gal is a possible target of IgE-mediated reactivity to antivenom.
abstract: BACKGROUND
  Antivenoms are mammalian immunoglobulins with the ability to neutralize snake venom components and to mitigate the progression of toxic effects. Immediate hypersensitivity to antivenoms often occurs during the first administration of these heterologous antibodies. A comparable clinical situation occurred after introduction of cetuximab, a chimeric mouse-human antibody, for cancer treatment. The carbohydrate epitope galactose-alpha-1,3-galactose, located on the Fab region of cetuximab, was identified as the target responsible for IgE reactivity.
  
  
  OBJECTIVE
  To investigate whether serum IgE antibodies directed to the α-gal epitope are associated with hypersensitivity to equine antivenoms.
  
  
  METHODS
  Antivenoms were screened for α-gal epitopes via immunoblot and in comparison with cetuximab and pork kidney by IgE reactivity assays. Basophil activation tests were used to investigate reactivity to antivenoms in samples from 20 patients with specific IgE antibodies to α-gal and 10 controls. Additional IgE detection, IgE inhibition, ImmunoCAP inhibition, and skin prick tests were performed using samples from selected patients.
  
  
  RESULTS
  Both antivenoms and cetuximab induced positive skin prick test results in patients with sIgE to α-gal. Alpha-gal epitopes were detected by immunoblotting on antivenoms. Measurements of IgE reactivity and ImmunoCAP inhibition indicated that the antivenoms contained lower α-gal contents than cetuximab. Deglycosylation assays and IgE inhibition tests confirmed that IgE-mediated reactivity to antivenom is associated with α-gal. Antivenoms, pork kidney, and cetuximab activated basophils from patients with IgE to α-gal.
  
  
  CONCLUSIONS
  Alpha-gal is a potential target of IgE-mediated reactivity to equine antivenom and a possible cause of the high incidence of hypersensitivity reactions during the first application of equine antivenom.
authors: Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors: J
authors: J
authors: Fischer
authors: Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors: B
authors: B
authors: Eberlein
authors: Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
authors: C
authors: http://orcid.org/0000-0001-9455-5442
authors: C
authors: Hilger
authors: Department of Clinical Toxicology, Technische Universität München, Munich, Germany.
authors: F
authors: F
authors: Eyer
authors: Center of Allergy and Environment, HMGU/Technische Universität München, Munich, Germany.
authors: S
authors: S
authors: Eyerich
authors: Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
authors: M
authors: M
authors: Ollert
authors: Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tuebingen, Tuebingen, Germany.|Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors: T
authors: T
authors: Biedermann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000997:Antivenins / Q000276:immunology*; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D000068818:Cetuximab / Q000009:adverse effects; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology; D005260:Female; D006736:Horses; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012882:Skin Tests; D060149:Tetraspanin 30 / Q000378:metabolism; D013954:Thyroglobulin / Q000276:immunology; D000519:alpha-Galactosidase / Q000276:immunology*
chemical_list: D000997:Antivenins; D015415:Biomarkers; D000939:Epitopes; D060149:Tetraspanin 30; D007073:Immunoglobulin E; D013954:Thyroglobulin; D000519:alpha-Galactosidase; D000068818:Cetuximab
keywords: anaphylaxis; antivenom; basophil activation test; snake venom; α-gal