PMID- 34143437
OWN - NLM
STAT- MEDLINE
DCOM- 20210914
LR  - 20220208
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 110
IP  - 3
DP  - 2021 Sep
TI  - Immunopharmacogenomics: Mechanisms of HLA-Associated Drug Reactions.
PG  - 607-615
LID - 10.1002/cpt.2343 [doi]
AB  - The human leukocyte antigen (HLA) system is the most polymorphic in the human 
      genome that has been associated with protection and predisposition to a broad 
      array of infectious, autoimmune, and malignant diseases. More recently over the 
      last two decades, HLA class I alleles have been strongly associated with 
      T-cell-mediated drug hypersensitivity reactions. In the case of abacavir 
      hypersensitivity and HLA-B*57:01, the 100% negative predictive value and low 
      number needed to test to prevent a single case has led to a durable and effective 
      global preprescription screening strategy. However, HLA associations are still 
      undefined for most drugs clinically associated with different delayed drug 
      hypersensitivity phenotypes, and an HLA association relevant to one population is 
      not generalizable across ethnicities. Furthermore, while a specific risk HLA 
      allele is necessary for drug-induced T-cell activation, it is not sufficient. The 
      low and incomplete positive predictive value has hindered efforts at clinical 
      implementation for many drugs but has provided the impetus to understand the 
      mechanisms of HLA class I restricted T-cell-mediated drug hypersensitivity 
      reactions. Current research has focused on defining the contribution of 
      additional elements of the adaptive immune response and other genetic and 
      ecologic risk factors that contribute to drug hypersensitivity risk. In this 
      review we focus on new insights into immunological, pharmacological, and genetic 
      mechanisms underpinning HLA-associated drug reactions and the implications for 
      future translation into clinical care.
CI  - (c) 2021 The Authors. Clinical Pharmacology & Therapeutics (c) 2021 American Society 
      for Clinical Pharmacology and Therapeutics.
FAU - Deshpande, Pooja
AU  - Deshpande P
AD  - Institute for Immunology and Infectious Diseases (IIID), Murdoch University, 
      Western Australia, Australia.
FAU - Hertzman, Rebecca J
AU  - Hertzman RJ
AD  - Institute for Immunology and Infectious Diseases (IIID), Murdoch University, 
      Western Australia, Australia.
FAU - Palubinsky, Amy M
AU  - Palubinsky AM
AD  - Department of Medicine, Vanderbilt University Medical Centre, Nashville, 
      Tennessee, USA.
FAU - Giles, Jason B
AU  - Giles JB
AD  - Department of Pharmacy Practice & Science, University of Arizona, Tucson, 
      Arizona, USA.
FAU - Karnes, Jason H
AU  - Karnes JH
AD  - Department of Medicine, Vanderbilt University Medical Centre, Nashville, 
      Tennessee, USA.
AD  - Department of Pharmacy Practice & Science, University of Arizona, Tucson, 
      Arizona, USA.
FAU - Gibson, Andrew
AU  - Gibson A
AD  - Institute for Immunology and Infectious Diseases (IIID), Murdoch University, 
      Western Australia, Australia.
FAU - Phillips, Elizabeth J
AU  - Phillips EJ
AD  - Institute for Immunology and Infectious Diseases (IIID), Murdoch University, 
      Western Australia, Australia.
AD  - Department of Medicine, Vanderbilt University Medical Centre, Nashville, 
      Tennessee, USA.
LA  - eng
GR  - R01 AI152183/AI/NIAID NIH HHS/United States
GR  - U01 AI154659/AI/NIAID NIH HHS/United States
GR  - P50 GM115305/GM/NIGMS NIH HHS/United States
GR  - T32 ES007091/ES/NIEHS NIH HHS/United States
GR  - R01 HG010863/HG/NHGRI NIH HHS/United States
GR  - K01 HL143137/HL/NHLBI NIH HHS/United States
GR  - R21 AI139021/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210717
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Adaptive Immunity/genetics/immunology
MH  - Alleles
MH  - Animals
MH  - Drug Hypersensitivity/*genetics/immunology
MH  - HLA Antigens/*genetics/immunology
MH  - HLA-B Antigens/genetics/immunology
MH  - Humans
MH  - Lymphocyte Activation/genetics/immunology
MH  - Pharmacogenetics/methods
MH  - T-Lymphocytes/immunology
PMC - PMC8500648
MID - NIHMS1744853
COIS- Conflicts of Interest. EJP is codirector of IIID Pty Ltd that holds a patent for 
      HLA-B*57:01 testing for abacavir hypersensitivity; she holds a provisional patent 
      for HLA-A*32:01 testing for vancomycin hypersensitivity. All other authors 
      declared no competing interests for this work.
EDAT- 2021/06/19 06:00
MHDA- 2021/09/15 06:00
PMCR- 2021/10/08
CRDT- 2021/06/18 12:31
PHST- 2021/04/09 00:00 [received]
PHST- 2021/06/13 00:00 [accepted]
PHST- 2021/06/19 06:00 [pubmed]
PHST- 2021/09/15 06:00 [medline]
PHST- 2021/06/18 12:31 [entrez]
PHST- 2021/10/08 00:00 [pmc-release]
AID - 10.1002/cpt.2343 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2021 Sep;110(3):607-615. doi: 10.1002/cpt.2343. Epub 2021 
      Jul 17.