Abstract
A growing number of associations between adverse drug reactions and alleles of the human leukocyte antigen (HLA) genes are now known. Although several models have been proposed to explain these associations, an underlying molecular basis has only recently been described. The associations between HLA-B*57:01 and abacavir hypersensitivity syndrome, and HLA-B*15:02 and carbamazepine-induced bullous skin disease have provided new insights into the mechanism associated with hypersensitivity reactions to these drugs. Here we discuss recent evidence that small molecules can interact with specific HLA to distort self-peptide presentation leading to autoimmune-like drug hypersensitivities that potentially provide clues to the mechanisms underlying other immunopathologies.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Anti-HIV Agents / adverse effects
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Anti-HIV Agents / therapeutic use
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Anticonvulsants / adverse effects
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Anticonvulsants / therapeutic use
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Antigen Presentation / drug effects
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Autoantigens / metabolism
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Carbamazepine / adverse effects
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Carbamazepine / therapeutic use
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Dideoxynucleosides / adverse effects
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Dideoxynucleosides / therapeutic use
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Drug Hypersensitivity / genetics
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Drug Hypersensitivity / immunology*
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HIV Infections / complications
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HIV Infections / drug therapy*
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HLA Antigens / immunology
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HLA Antigens / metabolism*
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Humans
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Peptide Fragments / metabolism
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Protein Binding / drug effects
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Seizures / drug therapy*
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Skin / drug effects*
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Skin / pathology
Substances
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Anti-HIV Agents
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Anticonvulsants
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Autoantigens
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Dideoxynucleosides
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HLA Antigens
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Peptide Fragments
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Carbamazepine
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abacavir