Go to page
 

Bibliographic Metadata

Title
Diclofenac hypersensitivity : antibody responses to the parent drug and relevant metabolites
AuthorHarrer, Andrea ; Lang, Roland ; Grims, Robert ; Braitsch, Michaela ; Hawranek, Thomas ; Aberer, Werner ; Vogel, Lothar ; Schmid, Walther ; Ferreira, Fatima ; Himly, Martin
Published in
PLoS ONE, Lawrence, Kan., 2010, Vol. 5, page 1-7
PublishedPublic Library of Science, 2010
LanguageEnglish
Document typeJournal Article
Keywords (EN)NSAIDs / Drug metabolism / Basophils / Enzyme-linked immunoassays / Hypersensitivity / Protein metabolism / Antibodies / Anaphylaxis
Project-/ReportnumberP18820-B13
ISSN1932-6203
URNurn:nbn:at:at-ubs:3-5915 Persistent Identifier (URN)
DOI10.1371/journal.pone.0013707 
Restriction-Information
 The work is publicly available
Files
Diclofenac hypersensitivity [0.32 mb]
Links
Reference
Classification
Abstract (English)

BACKGROUND:Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs) like diclofenac (DF) can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug- and/or metabolite-specific antibodies in selective DF hypersensitivity. METHODOLOGY/PRINCIPAL FINDINGS: DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14%) displayed drug/metabolite-specific IgG. CONCLUSIONS/SIGNIFICANCE: We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded.

Stats
The PDF-Document has been downloaded 13 times.
License
CC-BY-License (4.0)Creative Commons Attribution 4.0 International License