Abstract | BACKGROUND: 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.
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Authors | Andrea Harrer, Roland Lang, Robert Grims, Michaela Braitsch, Thomas Hawranek, Werner Aberer, Lothar Vogel, Walther Schmid, Fatima Ferreira, Martin Himly |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 10
Pg. e13707
(Oct 28 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21060839
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Antibodies
- Diclofenac
- Immunoglobulin E
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(adverse effects)
- Antibodies
(immunology)
- Basophils
(immunology)
- Diclofenac
(adverse effects)
- Drug Hypersensitivity
(immunology)
- Enzyme-Linked Immunosorbent Assay
- Female
- Humans
- Immunoglobulin E
(immunology)
- Mice
- Mice, Inbred BALB C
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