PMID- 30166701
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 0065-7778 (Print)
IS  - 0065-7778 (Linking)
VI  - 129
DP  - 2018
TI  - NEW STRATEGIES TO PREDICT AND PREVENT SERIOUS IMMUNOLOGICALLY MEDIATED ADVERSE 
      DRUG REACTIONS.
PG  - 74-87
AB  - Preventive efforts for serious immunologically mediated adverse drug reactions 
      (IM-ADRs) have been fueled by discovery of strong class I human leukocyte antigen 
      (HLA) associations; however, the low positive predictive value of HLA for IM-ADRs 
      has limited translation. Studies were undertaken to explain why most patients 
      carrying an HLA risk allele do not develop IM-ADR on exposure to the risk drug. 
      Tissue-specific approaches defined the T-cell receptor (TCR) repertoire and 
      phenotype of the pathogenic T cells found in the skin and blister fluid of 
      IM-ADRs. Dominant CD8+ T cell clonotypes representing >50% of total TCRalphabeta 
      sequences among CD8+ CD137+ T cells were identified in tissue to identify the 
      pathogenic activated T cells. Identification of the specific molecular and 
      cellular signatures of the antigen-driven pathogenic T cells will facilitate more 
      specific mechanisms to determine the small percentage of individuals carrying an 
      HLA risk allele who are likely to develop an IM-ADR before drug exposure.
FAU - Phillips, Elizabeth J
AU  - Phillips EJ
AD  - NASHVILLE, TENNESSEE.
LA  - eng
GR  - P30 AI110527/AI/NIAID NIH HHS/United States
GR  - P50 GM115305/GM/NIGMS NIH HHS/United States
GR  - R01 AI103348/AI/NIAID NIH HHS/United States
GR  - R13 AR071267/AR/NIAMS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Trans Am Clin Climatol Assoc
JT  - Transactions of the American Clinical and Climatological Association
JID - 7507559
RN  - 0 (Gout Suppressants)
RN  - 0 (HLA Antigens)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 63CZ7GJN5I (Allopurinol)
SB  - IM
MH  - Aged
MH  - Allopurinol/adverse effects/immunology
MH  - Animals
MH  - Drug Eruptions/genetics/immunology
MH  - Drug Hypersensitivity/genetics/*immunology/prevention & control
MH  - Drug-Related Side Effects and Adverse Reactions/genetics/immunology/prevention & 
      control
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Gout Suppressants/adverse effects/immunology
MH  - HLA Antigens/genetics/*immunology
MH  - Humans
MH  - Lymphocyte Activation/*drug effects
MH  - Phenotype
MH  - Receptors, Antigen, T-Cell/*drug effects/genetics/immunology
MH  - Risk Assessment
MH  - Risk Factors
MH  - T-Lymphocytes/*drug effects/immunology
PMC - PMC6116582
COIS- Potential Conflicts of Interest: Dr. Phillips is co-director of IIID Pty., Ltd., 
      that holds a patent for HLA-B*57:01 testing for abacavir hypersensitivity; and 
      has received grant funding from the National Institutes of Health: 
      1P50GM115305-01, 1RO1AI103348-01, 1P30AI110527-01A1, 1R13AR71267-01, and the 
      National Health & Medical Research Council of Australia.
EDAT- 2018/09/01 06:00
MHDA- 2018/12/12 06:00
PMCR- 2018/01/01
CRDT- 2018/09/01 06:00
PHST- 2018/09/01 06:00 [entrez]
PHST- 2018/09/01 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
PST - ppublish
SO  - Trans Am Clin Climatol Assoc. 2018;129:74-87.