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

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.