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Association of drug-serum protein adducts and anti-drug antibodies in dogs with sulphonamide hypersensitivity: a naturally occurring model of idiosyncratic drug toxicity.
Clin Exp Allergy. 2006 Jul; 36(7):907-15.CE

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.

Authors+Show Affiliations

Department of Medical Sciences, University of Wisconsin-Madison, Madison, WI 53706-1102, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16839406

Citation

Lavergne, S N., et al. "Association of Drug-serum Protein Adducts and Anti-drug Antibodies in Dogs With Sulphonamide Hypersensitivity: a Naturally Occurring Model of Idiosyncratic Drug Toxicity." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 36, no. 7, 2006, pp. 907-15.
Lavergne SN, Danhof RS, Volkman EM, et al. Association of drug-serum protein adducts and anti-drug antibodies in dogs with sulphonamide hypersensitivity: a naturally occurring model of idiosyncratic drug toxicity. Clin Exp Allergy. 2006;36(7):907-15.
Lavergne, S. N., Danhof, R. S., Volkman, E. M., & 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 and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 36(7), 907-15.
Lavergne SN, et al. Association of Drug-serum Protein Adducts and Anti-drug Antibodies in Dogs With Sulphonamide Hypersensitivity: a Naturally Occurring Model of Idiosyncratic Drug Toxicity. Clin Exp Allergy. 2006;36(7):907-15. PubMed PMID: 16839406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of drug-serum protein adducts and anti-drug antibodies in dogs with sulphonamide hypersensitivity: a naturally occurring model of idiosyncratic drug toxicity. AU - Lavergne,S N, AU - Danhof,R S, AU - Volkman,E M, AU - Trepanier,L A, PY - 2006/7/15/pubmed PY - 2007/2/23/medline PY - 2006/7/15/entrez SP - 907 EP - 15 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 36 IS - 7 N2 - 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. SN - 0954-7894 UR - https://www.unboundmedicine.com/medline/citation/16839406/Association_of_drug_serum_protein_adducts_and_anti_drug_antibodies_in_dogs_with_sulphonamide_hypersensitivity:_a_naturally_occurring_model_of_idiosyncratic_drug_toxicity_ L2 - https://doi.org/10.1111/j.1365-2222.2006.02506.x DB - PRIME DP - Unbound Medicine ER -