PATIENTS WITH DELAYED-ONSET SULFONAMIDE HYPERSENSITIVITY REACTIONS HAVE ANTIBODIES RECOGNIZING ENDOPLASMIC-RETICULUM LUMINAL PROTEINS

Sulfonamide antimicrobials cause a delayed-onset, hypersensitivity-typ e syndrome characterized by fever, skin rash and multiorgan toxicity o ccurring 7 to 14 days after initiation of therapy. The pathogenesis is believed to be immune-mediated. We investigated whether patients with delayed-onset sulfonamide hypersensitivity reactions had antibodies r ecognizing hapten-microsomal protein conjugates and/or native microsom al proteins. By immunoblotting using rat liver as a source of microsom al protein, 17 of 21 patients had antibodies recognizing one or more o f three native endoplasmic reticulum proteins of 55 kDa (14 of 21 pati ents), 80 kDa (4 of 21 patients) or 96 kDa (3 of 21 patients) in size on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No contr ol subjects (n = 11) and only 1 of 18 patients with adverse events not consistent with sulfonamide hypersensitivity reactions had antibodies against these microsomal proteins under the conditions used. Only 1 p atient had antibodies that recognized the sulfonamide hapten, sulfamet hoxazole. The 55-kDa protein was identified as protein disulfide isome rase. The 80-kDa protein was identified as grp78. The 96-kDa protein w as not identified. Delayed-onset sulfonamide hypersensitivity reaction s are therefore primarily associated with antibodies recognizing speci fic protein epitopes and not anti-drug antibodies.