Association of drug-serum protein adducts and anti-drug antibodies in dogs with sulphonamide hypersensitivity: A naturally occurring model of idiosyncratic drug toxicity

S. N. Lavergne, R. S. Danhof, E. M. Volkman, L. A. Trepanier

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sulphonamide antimicrobials, such as sulphamethoxazole (SMX), provide effective infection prophylaxis in immunocompromised patients, but can lead to drug hypersensitivity (HS) reactions. These reactions also occur in dogs, with a similar time course and clinical presentation as seen in humans. Objectives: Drug-serum adducts and anti-drug antibodies have been identified in sulphonamide HS humans. The aim of this study was to determine whether similar markers were present in dogs with sulphonamide HS. Methods: Thirty-four privately owned sulphonamide HS dogs, 10 sulphonamide-'tolerant' dogs, 18 sulphonamide-naïve dogs, and four dogs experimentally dosed with SMX and the oxidative metabolite SMX-nitroso, were tested for drug-serum adducts by immunoblotting, and anti-drug antibodies by ELISA. Results: Sulphonamide-serum adducts were found in 10/20 HS dogs tested (50%), but in no tolerant dogs. Anti-sulphonamide IgG antibodies were detected in 17/34 HS dogs (50%), but in only one tolerant dog; antibody absorbance values were significantly higher in HS dogs. There was a significant association between the presence of sulphonamide-serum adducts and anti-sulphonamide antibodies (P = 0.009). Anti-drug antibodies were also found in dogs experimentally dosed with SMX-nitroso followed by SMX, but not in a dog dosed with drug vehicle, followed by SMX. Conclusion: Similar humoral markers are present in dogs and humans with sulphonamide HS, supporting the use of dogs as a naturally occurring model for this syndrome in humans. These data suggest the potential use of drug-serum adducts and anti-drug antibodies as markers for sulphonamide HS. Preliminary data indicate that anti-sulphonamide antibodies may be triggered by the SMX-nitroso metabolite, not by the parent drug, in dogs.

Original languageEnglish (US)
Pages (from-to)907-915
Number of pages9
JournalClinical and Experimental Allergy
Volume36
Issue number7
DOIs
StatePublished - Jul 2006

Keywords

  • Anti-drug antibody
  • Drug adduct
  • Drug hypersensitivity
  • Sulphamethoxazole

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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