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Patients with delayed-onset sulfonamide hypersensitivity reactions have antibodies recognizing endoplasmic reticulum luminal proteins.
J Pharmacol Exp Ther. 1997 Aug; 282(2):1064-71.JP

Abstract

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.

Authors+Show Affiliations

Merck Research Laboratories, West Point, Pennsylvania, USA. acribb@upei.caNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9262376

Citation

Cribb, A E., et al. "Patients With Delayed-onset Sulfonamide Hypersensitivity Reactions Have Antibodies Recognizing Endoplasmic Reticulum Luminal Proteins." The Journal of Pharmacology and Experimental Therapeutics, vol. 282, no. 2, 1997, pp. 1064-71.
Cribb AE, Pohl LR, Spielberg SP, et al. Patients with delayed-onset sulfonamide hypersensitivity reactions have antibodies recognizing endoplasmic reticulum luminal proteins. J Pharmacol Exp Ther. 1997;282(2):1064-71.
Cribb, A. E., Pohl, L. R., Spielberg, S. P., & Leeder, J. S. (1997). Patients with delayed-onset sulfonamide hypersensitivity reactions have antibodies recognizing endoplasmic reticulum luminal proteins. The Journal of Pharmacology and Experimental Therapeutics, 282(2), 1064-71.
Cribb AE, et al. Patients With Delayed-onset Sulfonamide Hypersensitivity Reactions Have Antibodies Recognizing Endoplasmic Reticulum Luminal Proteins. J Pharmacol Exp Ther. 1997;282(2):1064-71. PubMed PMID: 9262376.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Patients with delayed-onset sulfonamide hypersensitivity reactions have antibodies recognizing endoplasmic reticulum luminal proteins. AU - Cribb,A E, AU - Pohl,L R, AU - Spielberg,S P, AU - Leeder,J S, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 1064 EP - 71 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 282 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9262376/Patients_with_delayed_onset_sulfonamide_hypersensitivity_reactions_have_antibodies_recognizing_endoplasmic_reticulum_luminal_proteins_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9262376 DB - PRIME DP - Unbound Medicine ER -