PMID- 30895730
OWN - NLM
STAT- MEDLINE
DCOM- 20200708
LR  - 20200708
IS  - 2059-2310 (Electronic)
IS  - 2059-2302 (Linking)
VI  - 93
IP  - 6
DP  - 2019 Jun
TI  - HLA-associated antiepileptic drug-induced cutaneous adverse reactions.
PG  - 417-435
LID - 10.1111/tan.13530 [doi]
AB  - Adverse drug reactions (ADRs) are a common cause of hospital admissions (up to 
      19%), with the majority of cases due to off-target predictable drug effects (type 
      A reactions). However, idiosyncratic drug-induced immune activated (type B) 
      reactions contribute to a range of hypersensitivity reactions, with 
      T-cell-mediated type IV hypersensitivity reactions mainly manifesting as 
      cutaneous ADRs (cADRs). Aromatic antiepileptic drugs (AEDs), used in the 
      treatment of epilepsy as well as bipolar disorder or neuropathic pain, have been 
      implicated as culprit drugs in a spectrum of pathologies ranging from mild 
      maculopapular exanthema (MPE) to severe and life-threatening conditions including 
      drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson 
      syndrome (SJS) and toxic epidermal necrolysis (TEN). These AED-induced cADRs are 
      unpredictable based on pharmacological and clinical factors alone, thereby 
      prompting investigations into genomic contributors mediating risk of pathology. 
      The most strongly associated risk genes identified are from the human leukocyte 
      antigen (HLA) class I alleles, which play a critical role in adaptive immunity by 
      flagging either infected or aberrant cells for recognition by surveying T-cells. 
      In the setting of drug hypersensitivity, the immunogenicity of HLA molecules and 
      their peptide cargo can be modulated by interactions with small drug molecules 
      that drive inappropriate T-cell responses. This review discusses the current 
      understanding of HLA class I molecules in modifying risk of AED-induced cADRs.
CI  - (c) 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Mullan, Kerry A
AU  - Mullan KA
AUID- ORCID: 0000-0003-4400-1198
AD  - Infection and Immunity Program, Monash Biomedicine Discovery Institute and 
      Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria, Australia.
FAU - Anderson, Alison
AU  - Anderson A
AD  - Department of Neuroscience, Central Clinical School, Monash University, Clayton, 
      Victoria, Australia.
FAU - Illing, Patricia T
AU  - Illing PT
AUID- ORCID: 0000-0002-3870-0796
AD  - Infection and Immunity Program, Monash Biomedicine Discovery Institute and 
      Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria, Australia.
FAU - Kwan, Patrick
AU  - Kwan P
AD  - Department of Neuroscience, Central Clinical School, Monash University, Clayton, 
      Victoria, Australia.
AD  - Department of Neuroscience, The Alfred Hospital, Melbourne, Victoria, Australia.
FAU - Purcell, Anthony W
AU  - Purcell AW
AD  - Infection and Immunity Program, Monash Biomedicine Discovery Institute and 
      Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria, Australia.
FAU - Mifsud, Nicole A
AU  - Mifsud NA
AUID- ORCID: 0000-0001-8647-2102
AD  - Infection and Immunity Program, Monash Biomedicine Discovery Institute and 
      Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria, Australia.
LA  - eng
GR  - 1103979/National Health and Medical Research Council/International
GR  - 1122099/National Health and Medical Research Council/International
GR  - Medical Research Future Fund Practitioner Fellowship/International
GR  - National Health and Medical Research Council (NHMRC) Principal Research 
      Fellowship/International
GR  - Australian Government Research Training Program (RTP)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190409
PL  - England
TA  - HLA
JT  - HLA
JID - 101675570
RN  - 0 (Anticonvulsants)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Alleles
MH  - Anticonvulsants/*adverse effects
MH  - Drug Hypersensitivity/*genetics/immunology
MH  - Epilepsy
MH  - Exanthema/genetics/immunology
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - Genetic Linkage
MH  - HLA Antigens/*genetics
MH  - HLA-A Antigens/genetics
MH  - HLA-B Antigens/genetics
MH  - Humans
MH  - Patient Admission
MH  - Polymorphism, Genetic
MH  - Risk Factors
MH  - Skin/*drug effects/immunology
MH  - Stevens-Johnson Syndrome/genetics/immunology
MH  - T-Lymphocytes/immunology
OTO - NOTNLM
OT  - adverse drug reaction
OT  - carbamazepine
OT  - genomics
OT  - human leukocyte antigen
OT  - lamotrigine
OT  - oxcarbazepine
OT  - phenytoin
OT  - transcriptomics
EDAT- 2019/03/22 06:00
MHDA- 2020/07/09 06:00
CRDT- 2019/03/22 06:00
PHST- 2018/11/11 00:00 [received]
PHST- 2019/02/20 00:00 [revised]
PHST- 2019/03/18 00:00 [accepted]
PHST- 2019/03/22 06:00 [pubmed]
PHST- 2020/07/09 06:00 [medline]
PHST- 2019/03/22 06:00 [entrez]
AID - 10.1111/tan.13530 [doi]
PST - ppublish
SO  - HLA. 2019 Jun;93(6):417-435. doi: 10.1111/tan.13530. Epub 2019 Apr 9.