PMID- 22987284
OWN - NLM
STAT- MEDLINE
DCOM- 20130404
LR  - 20220330
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 57
IP  - 2
DP  - 2013 Feb
TI  - Human leukocyte antigen (HLA)-B*57:01-restricted activation of drug-specific T 
      cells provides the immunological basis for flucloxacillin-induced liver injury.
PG  - 727-39
LID - 10.1002/hep.26077 [doi]
AB  - The role of the adaptive immune system in adverse drug reactions that target the 
      liver has not been defined. For flucloxacillin, a delay in the reaction onset and 
      identification of human leukocyte antigen (HLA)-B*57:01 as a susceptibility 
      factor are indicative of an immune pathogenesis. Thus, we characterize 
      flucloxacillin-responsive CD4+ and CD8+ T cells from patients with liver injury 
      and show that naive CD45RA+CD8+ T cells from volunteers expressing HLA-B*57:01 
      are activated with flucloxacillin when dendritic cells present the drug antigen. 
      T-cell clones expressing CCR4 and CCR9 migrated toward CCL17 and CCL 25, and 
      secreted interferon-gamma (IFN-gamma), T helper (Th)2 cytokines, perforin, granzyme 
      B, and FasL following drug stimulation. Flucloxacillin bound covalently to 
      selective lysine residues on albumin in a time-dependent manner and the level of 
      binding correlated directly with the stimulation of clones. Activation of CD8+ 
      clones with flucloxacillin was processing-dependent and restricted by HLA-B*57:01 
      and the closely related HLA-B*58:01. Clones displayed additional reactivity 
      against beta-lactam antibiotics including oxacillin, cloxacillin, and dicloxacillin, 
      but not abacavir or nitroso sulfamethoxazole. CONCLUSION: This work defines the 
      immune basis for flucloxacillin-induced liver injury and links the genetic 
      association to the iatrogenic disease.
CI  - Copyright (c) 2012 American Association for the Study of Liver Diseases.
FAU - Monshi, Manal M
AU  - Monshi MM
AD  - MRC Centre for Drug Safety Science, Department of Pharmacology, University of 
      Liverpool, Liverpool, UK.
FAU - Faulkner, Lee
AU  - Faulkner L
FAU - Gibson, Andrew
AU  - Gibson A
FAU - Jenkins, Rosalind E
AU  - Jenkins RE
FAU - Farrell, John
AU  - Farrell J
FAU - Earnshaw, Caroline J
AU  - Earnshaw CJ
FAU - Alfirevic, Ana
AU  - Alfirevic A
FAU - Cederbrant, Karin
AU  - Cederbrant K
FAU - Daly, Ann K
AU  - Daly AK
FAU - French, Neil
AU  - French N
FAU - Pirmohamed, Munir
AU  - Pirmohamed M
FAU - Park, B Kevin
AU  - Park BK
FAU - Naisbitt, Dean J
AU  - Naisbitt DJ
LA  - eng
GR  - G0700654/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (CC chemokine receptor 9)
RN  - 0 (CCR4 protein, human)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B57 antigen)
RN  - 0 (HLA-B58 antigen)
RN  - 0 (Receptors, CCR)
RN  - 0 (Receptors, CCR4)
RN  - 0 (Serum Albumin)
RN  - 43B2M34G2V (Floxacillin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Movement/drug effects
MH  - Chemical and Drug Induced Liver Injury/*etiology/immunology
MH  - Clone Cells/immunology
MH  - Female
MH  - Floxacillin/*adverse effects/metabolism
MH  - HLA-B Antigens/immunology/*physiology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Leukocytes, Mononuclear/drug effects/immunology
MH  - Lymphocyte Activation/drug effects/*immunology
MH  - Lysine/metabolism
MH  - Male
MH  - Middle Aged
MH  - Receptors, CCR/biosynthesis
MH  - Receptors, CCR4/biosynthesis
MH  - Serum Albumin/metabolism
EDAT- 2012/09/19 06:00
MHDA- 2013/04/05 06:00
CRDT- 2012/09/19 06:00
PHST- 2012/07/10 00:00 [received]
PHST- 2012/09/04 00:00 [accepted]
PHST- 2012/09/19 06:00 [entrez]
PHST- 2012/09/19 06:00 [pubmed]
PHST- 2013/04/05 06:00 [medline]
AID - 10.1002/hep.26077 [doi]
PST - ppublish
SO  - Hepatology. 2013 Feb;57(2):727-39. doi: 10.1002/hep.26077.