Document Detail


Suppression of gastric acid increases the risk of developing immunoglobulin E-mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model.
MedLine Citation:
PMID:  19817752     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Hypersensitivity reactions towards non-steroidal anti-inflammatory drugs (NSAID) are common, although true allergies are detectable only in a subgroup of patients. The current study was prompted by a case observation, where a patient experienced generalized urticaria following his second course of diclofenac and proton pump inhibitor medication, and was found to have diclofenac-specific IgE. During recent years, our group has been investigating the importance of gastric digestion in the development of food allergies, demonstrating anti-acid medication as a risk factor for sensitization against food proteins.
OBJECTIVE: Here, we aimed to investigate whether the mechanism of food allergy induction described can also be causative in NSAID allergy, using diclofenac as a paradigm.
METHODS: We subjected BALB/c mice to several oral immunization regimens modelled after the patient's medication intake. Diclofenac was applied with or without gastric acid suppression, in various doses, alone or covalently coupled to albumin, a protein abundant in gastric juices. Immune responses were assessed on the antibody level, and functionally examined by in vitro and in vivo crosslinking assays.
RESULTS: Only mice receiving albumin-coupled diclofenac under gastric acid suppression developed anti-diclofenac IgG1 and IgE, whereas no immune responses were induced by the drug alone or without gastric acid suppression. Antibody induction was dose dependent with the group receiving the higher dose of the drug showing sustained anti-diclofenac titres. The antibodies induced triggered basophil degranulation in vitro and positive skin tests in vivo.
CONCLUSION: Gastric acid suppression was found to be a causative mechanism in the induction of IgE-mediated diclofenac allergy.
Authors:
A B Riemer; S Gruber; I Pali-Schöll; T Kinaciyan; E Untersmayr; E Jensen-Jarolim
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-07
Journal Detail:
Title:  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology     Volume:  40     ISSN:  1365-2222     ISO Abbreviation:  Clin. Exp. Allergy     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-11-15     Revised Date:  2013-02-27    
Medline Journal Info:
Nlm Unique ID:  8906443     Medline TA:  Clin Exp Allergy     Country:  England    
Other Details:
Languages:  eng     Pagination:  486-93     Citation Subset:  IM    
Affiliation:
Department of Pathophysiology, Medical University of Vienna, Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antacids / adverse effects,  pharmacology
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage,  adverse effects*,  immunology
Antibodies / analysis
Antigen-Antibody Reactions
Diclofenac / administration & dosage,  adverse effects*,  immunology
Disease Models, Animal*
Drug Hypersensitivity / etiology,  immunology*
Enzyme-Linked Immunosorbent Assay
Female
Gastric Acid / secretion*
Humans
Immunoglobulin E / immunology*
Male
Mice
Mice, Inbred BALB C
Middle Aged
Risk Factors
Skin Tests
Grant Support
ID/Acronym/Agency:
F 1808-B13//Austrian Science Fund FWF
Chemical
Reg. No./Substance:
0/Antacids; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antibodies; 15307-86-5/Diclofenac; 37341-29-0/Immunoglobulin E
Comments/Corrections
Comment In:
Clin Exp Allergy. 2010 Mar;40(3):362-4   [PMID:  19930440 ]

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