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Review
. 2009 Mar;84(3):268-72.
doi: 10.4065/84.3.268.

Mechanisms of drug-induced allergy

Benno Schnyder  1 , Werner J Pichler
Affiliations
Review

Mechanisms of drug-induced allergy

Benno Schnyder et al. Mayo Clin Proc. 2009 Mar.

Abstract

We identified English-language publications on hypersensitivity reactions to xenobiotics through the PubMed database, using the search terms drug and/or xenobiotic, hypersensitivity reaction, mechanism, and immune mediated. We analyzed articles pertaining to the mechanism and the role of T cells. Immune hypersensitivity reactions to drugs are mediated predominantly by IgE antibodies or T cells. The mechanism of IgE-mediated reactions is well investigated, but the mechanisms of T-cell-mediated drug hypersensitivity are not well understood. The literature describes 2 concepts: the hapten/prohapten concept and the concept of pharmacological interactions of drugs with immune receptors. In T-cell-mediated allergic drug reactions, the specificity of the T-cell receptor that is stimulated by the drug may often be directed to a cross-reactive major histocompatibility complex-peptide compound. Thus, previous contact with the causative drug is not obligatory, and an immune mechanism should be considered as the cause of hypersensitivity, even in reactions that occur on primary exposure. Indeed, immune-mediated reactions to xenobiotics in patients without prior exposure to the agent have been described recently for radiocontrast media and neuromuscular blocking agents. Thus, the "allergenic" potential of a drug under development should be evaluated not only by screening its haptenlike characteristics but also by assessing its direct immunostimulatory potential.

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Figures

FIGURE 1.
FIGURE 1.
Specific T-cell recognition of drug-carrier compounds (hapten/prohapten concept). Drug/drug-metabolite carrier compounds are presented on antigen-presenting cells (APCs), where T cells with appropriate T-cell receptors (TCRs) recognize them. MHC = major histocompatibility complex.
FIGURE 2.
FIGURE 2.
Stimulation of specific T cells by a native drug (the concept of pharmacological interactions of drugs with immune receptors). Memory T cells (TMEMORY) with a certain sensitization may be stimulated by an interaction of a native drug with the T-cell receptor (TCR), supplemented by the interaction with a fitting major histocompatibility complex (MHC) molecule. APC = antigen-presenting cell.
See this image and copyright information in PMC

Comment in

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