PMID- 27879435
OWN - NLM
STAT- MEDLINE
DCOM- 20171214
LR  - 20181113
IS  - 1533-1601 (Electronic)
IS  - 0192-6233 (Print)
IS  - 0192-6233 (Linking)
VI  - 45
IP  - 1
DP  - 2017 Jan
TI  - Identification of MHC Haplotypes Associated with Drug-induced Hypersensitivity 
      Reactions in Cynomolgus Monkeys.
PG  - 127-133
LID - 10.1177/0192623316677326 [doi]
AB  - Drug-induced hypersensitivity reactions can significantly impact drug development 
      and use. Studies to understand risk factors for drug-induced hypersensitivity 
      reactions have identified genetic association with specific human leukocyte 
      antigen (HLA) alleles. Interestingly, drug-induced hypersensitivity reactions can 
      occur in nonhuman primates; however, association between drug-induced 
      hypersensitivity reactions and major histocompatibility complex (MHC) alleles has 
      not been described. In this study, tissue samples were collected from 62 
      cynomolgus monkeys from preclinical studies in which 9 animals had evidence of 
      drug-induced hypersensitivity reactions. Microsatellite analysis was used to 
      determine MHC haplotypes for each animal. A total of 7 haplotypes and recombinant 
      MHC haplotypes were observed, with distribution frequency comparable to known MHC 
      I allele frequency in cynomolgus monkeys. Genetic association analysis identified 
      alleles from the M3 haplotype of the MHC I B region (B*011:01, B*075:01, 
      B*079:01, B*070:02, B*098:05, and B*165:01) to be significantly associated (chi(2) 
      test for trend, p < 0.05) with occurrence of drug-induced hypersensitivity 
      reactions. Sequence similarity from alignment of alleles in the M3 haplotype B 
      region and HLA alleles associated with drug-induced hypersensitivity reactions in 
      humans was 86% to 93%. These data demonstrate that MHC alleles in cynomolgus 
      monkeys are associated with drug-induced hypersensitivity reactions, similar to 
      HLA alleles in humans.
FAU - Wu, Hong
AU  - Wu H
AD  - 1 Pfizer, Drug Safety Research and Development, Groton, Connecticut, USA.
FAU - Whritenour, Jessica
AU  - Whritenour J
AD  - 1 Pfizer, Drug Safety Research and Development, Groton, Connecticut, USA.
FAU - Sanford, Jonathan C
AU  - Sanford JC
AD  - 1 Pfizer, Drug Safety Research and Development, Groton, Connecticut, USA.
FAU - Houle, Christopher
AU  - Houle C
AD  - 1 Pfizer, Drug Safety Research and Development, Groton, Connecticut, USA.
FAU - Adkins, Karissa K
AU  - Adkins KK
AD  - 1 Pfizer, Drug Safety Research and Development, Groton, Connecticut, USA.
LA  - eng
GR  - C06 RR015459/RR/NCRR NIH HHS/United States
GR  - C06 RR020141/RR/NCRR NIH HHS/United States
GR  - P51 RR000167/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20161123
PL  - United States
TA  - Toxicol Pathol
JT  - Toxicologic pathology
JID - 7905907
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Drug Evaluation, Preclinical
MH  - Drug Hypersensitivity/*genetics
MH  - Haplotypes
MH  - Histocompatibility Antigens Class I/genetics
MH  - Histocompatibility Antigens Class II/genetics
MH  - Macaca fascicularis/*genetics
MH  - Major Histocompatibility Complex/*genetics
MH  - Microsatellite Repeats
MH  - Sequence Analysis, DNA
PMC - PMC5225012
MID - NIHMS823197
OTO - NOTNLM
OT  - MHC
OT  - cynomolgus monkey
OT  - drug-induced hypersensitivity reaction
OT  - haplotype
EDAT- 2016/11/24 06:00
MHDA- 2017/12/15 06:00
PMCR- 2018/01/01
CRDT- 2016/11/24 06:00
PHST- 2016/11/24 06:00 [pubmed]
PHST- 2017/12/15 06:00 [medline]
PHST- 2016/11/24 06:00 [entrez]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 0192623316677326 [pii]
AID - 10.1177/0192623316677326 [doi]
PST - ppublish
SO  - Toxicol Pathol. 2017 Jan;45(1):127-133. doi: 10.1177/0192623316677326. Epub 2016 
      Nov 23.