Alpha-gal is a possible target of IgE-mediated reactivity to antivenom.
- Molecular and Translational Allergology
- Allergy and Clinical Immunology
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 alpha-gal epitope are associated with hypersensitivity to equine antivenoms. METHODS: Antivenoms were screened for alpha-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 alpha-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 alpha-gal. Alpha-gal epitopes were detected by immunoblotting on antivenoms. Measurements of IgE reactivity and ImmunoCAP inhibition indicated that the antivenoms contained lower alpha-gal contents than cetuximab. Deglycosylation assays and IgE inhibition tests confirmed that IgE-mediated reactivity to antivenom is associated with alpha-gal. Antivenoms, pork kidney, and cetuximab activated basophils from patients with IgE to alpha-gal. CONCLUSION: 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.