Anti-myeloperoxidase and anti-cathepsin G antibodies in sulphonamide hypersensitivity.

BACKGROUND

Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis in humans. Sulphonamide antimicrobials cause drug hypersensitivity (HS) reactions with some clinical signs that are suggestive of vasculitis.

OBJECTIVE

The purpose of this study was to determine whether sulphonamide HS is associated with anti-neutrophil antibodies, using the dog as a spontaneous clinical model.

METHODS

Thirty-four sulphonamide-HS dogs, 11 sulphonamide-'tolerant' dogs, and nine healthy sulphonamide-naïve dogs were evaluated for anti-neutrophil antibodies using a commercial ELISA against human myeloperoxidase (MPO), a commercial human ANCA Western blot protocol, and immunoblotting against whole canine neutrophils.

RESULTS

Using ELISA, anti-MPO antibodies were found with an apparent higher frequency in HS dogs (50%), compared with 'tolerant' dogs (18%), which also showed significantly lower absorbances. Among HS dogs, anti-MPO antibodies were significantly more common, with significantly higher absorbances, in dogs that did not survive the HS reaction (78%) compared with survivors (35%). Using immunoblotting, ANCA were detected with similar overall frequencies in HS and 'tolerant' dogs. However, one protein targeted by several HS dogs, but no 'tolerant' dogs, was identified as cathepsin G.

CONCLUSION

These data indicate that anti-MPO antibodies and anti-cathepsin G antibodies are associated with sulphonamide HS. Anti-MPO antibodies have been shown to be pathogenic both in vitro and in vivo, leading to vasculitis lesions and vasculitis-like syndromes. The present study therefore suggests that vasculitis might be one mechanism of tissue damage in this sulphonamide HS. Furthermore, the evaluation of ANCA, and its relationship to disease severity and clinical outcome, should be considered in human patients with sulphonamide drug HS.