RT Journal Article
SR Electronic
T1 Patients with Delayed-Onset Sulfonamide Hypersensitivity Reactions Have Antibodies Recognizing Endoplasmic Reticulum Luminal Proteins
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1064
OP 1072
VO 282
IS 2
A1 Alastair E. Cribb
A1 Lance R. Pohl
A1 Stephen P. Spielberg
A1 J. Steven Leeder
YR 1997
UL http://jpet.aspetjournals.org/content/282/2/1064.abstract
AB Sulfonamide antimicrobials cause a delayed-onset, hypersensitivity-type syndrome characterized by fever, skin rash and multiorgan toxicity occurring 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 recognizing hapten-microsomal protein conjugates and/or native microsomal proteins. By immunoblotting using rat liver as a source of microsomal protein, 17 of 21 patients had antibodies recognizing one or more of three native endoplasmic reticulum proteins of 55 kDa (14 of 21 patients), 80 kDa (4 of 21 patients) or 96 kDa (3 of 21 patients) in size on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No control 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 patient had antibodies that recognized the sulfonamide hapten, sulfamethoxazole. The 55-kDa protein was identified as protein disulfide isomerase. The 80-kDa protein was identified as grp78. The 96-kDa protein was not identified. Delayed-onset sulfonamide hypersensitivity reactions are therefore primarily associated with antibodies recognizing specific protein epitopes and not anti-drug antibodies. The American Society for Pharmacology and Experimental Therapeutics