PMID- 29150704
OWN - NLM
STAT- MEDLINE
DCOM- 20190510
LR  - 20190510
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 92
IP  - 3
DP  - 2018 Mar
TI  - Evaluation of immune-mediated idiosyncratic drug toxicity using chimeric HLA 
      transgenic mice.
PG  - 1177-1188
LID - 10.1007/s00204-017-2112-9 [doi]
AB  - Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug 
      reaction, potentially resulting in death. Although genome-wide association 
      studies suggest that the occurrence of immune-mediated IDT is strongly associated 
      with specific human leukocyte antigen (HLA) allotypes, these associations have 
      not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 
      and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice 
      carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may 
      be useful for evaluating immune-mediated IDT. Local lymph node assay (LLNA) 
      results demonstrated that percentages of BrdU(+), IL-2(+), and IFN-gamma(+) in CD8(+) 
      T cells of ABC (50 mg/kg/day)-applied B*57:01-Tg mice were significantly higher 
      than those in littermates (LMs), resulting in the infiltration of inflammatory 
      cells into the ear. These immune responses were not observed in B*57:03-Tg mice 
      (negative control). Furthermore, oral administration of 1% (v/v) ABC 
      significantly increased the percentage of CD44(high)CD62L(low) CD8(+) memory T 
      cells in lymph nodes and spleen derived from B*57:01-Tg mice, but not in those 
      from B*57:03-Tg mice and LMs. These results suggest that B*57:01-Tg mice 
      potentially enable the reproduction and evaluation of HLA-B*57:01 and ABC-induced 
      immune-mediated IDT.
FAU - Susukida, Takeshi
AU  - Susukida T
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
FAU - Aoki, Shigeki
AU  - Aoki S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
FAU - Kogo, Kotaro
AU  - Kogo K
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
FAU - Fujimori, Sota
AU  - Fujimori S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
FAU - Song, Binbin
AU  - Song B
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
FAU - Liu, Cong
AU  - Liu C
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
FAU - Sekine, Shuichi
AU  - Sekine S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
FAU - Ito, Kousei
AU  - Ito K
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan. itokousei@chiba-u.jp.
LA  - eng
GR  - 15K14995/Japan Society for the Promotion of Science/
GR  - 15H04661/Japan Society for the Promotion of Science/
GR  - 25670068/Japan Society for the Promotion of Science/
GR  - 24390037/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20171117
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Dideoxynucleosides)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*57:01 antigen)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/drug effects/immunology
MH  - Dideoxynucleosides/administration & dosage/*adverse effects/toxicity
MH  - Drug-Related Side Effects and Adverse Reactions/*immunology
MH  - HLA-B Antigens/genetics/*immunology
MH  - Humans
MH  - Lymph Nodes/drug effects/immunology
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Toxicity Tests/*methods
OTO - NOTNLM
OT  - Abacavir
OT  - Human leucocyte antigen
OT  - Idiosyncratic drug toxicity
OT  - Immunotoxicology
OT  - In vivo model
EDAT- 2017/11/19 06:00
MHDA- 2019/05/11 06:00
CRDT- 2017/11/19 06:00
PHST- 2017/09/01 00:00 [received]
PHST- 2017/11/08 00:00 [accepted]
PHST- 2017/11/19 06:00 [pubmed]
PHST- 2019/05/11 06:00 [medline]
PHST- 2017/11/19 06:00 [entrez]
AID - 10.1007/s00204-017-2112-9 [pii]
AID - 10.1007/s00204-017-2112-9 [doi]
PST - ppublish
SO  - Arch Toxicol. 2018 Mar;92(3):1177-1188. doi: 10.1007/s00204-017-2112-9. Epub 2017 
      Nov 17.