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.


OBJECTIVE
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.


CONCLUSIONS
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.
Lavergne
S N
SN
Department of Medical Sciences, University of Wisconsin-Madison, Madison, WI 53706-1102, USA.
Danhof
R S
RS
Volkman
E M
EM
Trepanier
L A
LA
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000276:immunology / Q000633:toxicity*; D000918:Antibody Specificity; D001798:Blood Proteins / Q000378:metabolism*; D003429:Cross Reactions; D004195:Disease Models, Animal; D004285:Dogs; D004342:Drug Hypersensitivity / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D011485:Protein Binding; D013420:Sulfamethoxazole / Q000276:immunology; D013449:Sulfonamides / Q000097:blood / Q000276:immunology / Q000633:toxicity*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000276:immunology
D000890:Anti-Infective Agents; D001798:Blood Proteins; D007074:Immunoglobulin G; D013449:Sulfonamides; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013420:Sulfamethoxazole