PMID- 28017537
OWN - NLM
STAT- MEDLINE
DCOM- 20170818
LR  - 20220129
IS  - 1880-0920 (Electronic)
IS  - 1347-4367 (Linking)
VI  - 32
IP  - 1
DP  - 2017 Feb
TI  - Human leukocyte antigen and idiosyncratic adverse drug reactions.
PG  - 21-30
LID - S1347-4367(16)30078-7 [pii]
LID - 10.1016/j.dmpk.2016.11.003 [doi]
AB  - A clinical association between a specific human leukocyte antigen (HLA) allele 
      and idiosyncratic adverse drug reactions (IADRs) is a strong indication that 
      IADRs are mediated by the adaptive immune system. For example, it is 
      well-established that HLA-B*15:02 and HLA-B*57:01 are associated with 
      carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis 
      (TEN) and abacavir-induced hypersensitivity/flucloxacillin-induced liver injury, 
      respectively. Drug-specific T-cells whose response is restricted by specific HLA 
      risk alleles have been detected from IADR patients, also suggesting an adaptive 
      immune pathogenesis. T-cells from carbamazepine SJS/TEN patients are activated by 
      direct pharmacological interaction between carbamazepine and HLA-B*15:02 
      expressed on antigen presenting cells (APCs). Abacavir-specific, 
      HLA-B*57:01-restricted T-cells are activated by APCs presenting peptides which 
      are only displayed by the HLA molecule when abacavir is bound during peptide 
      loading. Finally, HLA-B*57:01-restricted activation of T-cells from patients with 
      flucloxacillin-induced liver injury is dependent on processing of drug protein 
      adducts. Based on these observations, it is now possible to utilize blood from 
      healthy drug-naive volunteers to study the priming of naive T-cells to drugs. 
      Future development of these methodologies may lead to the development of assays 
      that predict intrinsic immunogenicity of drugs and chemicals at the preclinical 
      stage of drug development.
CI  - Copyright (c) 2016 The Japanese Society for the Study of Xenobiotics. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Usui, Toru
AU  - Usui T
AD  - Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 
      Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
FAU - Naisbitt, Dean J
AU  - Naisbitt DJ
AD  - MRC Centre for Drug Safety Science, Department of Pharmacology, University of 
      Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, England, UK. 
      Electronic address: dnes@liverpool.ac.uk.
LA  - eng
GR  - MR/L006758/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Review
DEP - 20161118
PL  - England
TA  - Drug Metab Pharmacokinet
JT  - Drug metabolism and pharmacokinetics
JID - 101164773
RN  - 0 (HLA Antigens)
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Alleles
MH  - Drug-Related Side Effects and Adverse Reactions/genetics/*immunology
MH  - HLA Antigens/genetics/*immunology
MH  - Humans
MH  - *Pharmaceutical Preparations
OTO - NOTNLM
OT  - Altered peptide repertory concept
OT  - Drug-induced liver injury
OT  - Hapten concept
OT  - Hepersensitivity
OT  - Human leukocyte antigen
OT  - Reactive metabolites
OT  - Severe cutaneous adverse reactions
OT  - p-i concept
EDAT- 2016/12/27 06:00
MHDA- 2017/08/19 06:00
CRDT- 2016/12/27 06:00
PHST- 2016/09/07 00:00 [received]
PHST- 2016/11/08 00:00 [revised]
PHST- 2016/11/09 00:00 [accepted]
PHST- 2016/12/27 06:00 [pubmed]
PHST- 2017/08/19 06:00 [medline]
PHST- 2016/12/27 06:00 [entrez]
AID - S1347-4367(16)30078-7 [pii]
AID - 10.1016/j.dmpk.2016.11.003 [doi]
PST - ppublish
SO  - Drug Metab Pharmacokinet. 2017 Feb;32(1):21-30. doi: 10.1016/j.dmpk.2016.11.003. 
      Epub 2016 Nov 18.