Funding: This study was funded by a grant from the National Institutes of Health, GM 61753.
Association of drug-serum protein adducts and anti-drug antibodies in dogs with sulphonamide hypersensitivity: A naturally occurring model of idiosyncratic drug toxicity
Article first published online: 31 MAY 2006
Clinical & Experimental Allergy
Volume 36, Issue 7, pages 907–915, July 2006
How to Cite
Lavergne, S. N., Danhof, R. S., Volkman, E. M. and Trepanier, L. A. (2006), Association of drug-serum protein adducts and anti-drug antibodies in dogs with sulphonamide hypersensitivity: A naturally occurring model of idiosyncratic drug toxicity. Clinical & Experimental Allergy, 36: 907–915. doi: 10.1111/j.1365-2222.2006.02506.x
- Issue published online: 31 MAY 2006
- Article first published online: 31 MAY 2006
- Submitted 20 December 2005; revised 10 February 2006; accepted 27 March 2006
- anti-drug antibody;
- drug adduct;
- drug hypersensitivity;
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.