PMID- 35568130
OWN - NLM
STAT- MEDLINE
DCOM- 20220606
LR  - 20220606
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 82
DP  - 2022 Aug
TI  - Weak complex formation of adverse drug reaction-associated HLAB57, B58, and B15 
      molecules.
PG  - 105383
LID - S0887-2333(22)00080-7 [pii]
LID - 10.1016/j.tiv.2022.105383 [doi]
AB  - The combination of certain human leukocyte antigen (HLA) polymorphisms with 
      administration of certain drugs shows a strong correlation with developing drug 
      hypersensitivity. Examples of typical combinations are HLA-B*57:01 with abacavir 
      and HLA-B*15:02 with carbamazepine. However, despite belonging to the same 
      serotype, HLA-B*57:03 and HLA-B*15:01 are not associated with drug 
      hypersensitivity. Recent studies have shown that several HLA polymorphisms are 
      associated with multiple drugs rather than a single drug, all resulting in drug 
      hypersensitivity. In this study, we compared the molecular structures and 
      intracellular localization of HLA-B*57:01, HLA-B*58:01, and HLA-B*15:02, which 
      pose risks for developing drug hypersensitivity, as well as HLA-B*57:03 and 
      HLA-B*15:01 that do not present such risks. We found that HLA molecules posing 
      risks have a low affinity for the subunit beta(2)-microglobulin; notably, the weak 
      hydrogen bond formed via Gln96 of the HLA molecule contributes to this behavior. 
      We also clarified that these HLA molecules are easily accumulated in the 
      endoplasmic reticulum, exhibiting a low expression on the cell surface. 
      Considering that these hypersensitivity risk-associated HLA molecules form 
      complexes with beta(2)-microglobulin and peptides in the endoplasmic reticulum, we 
      assumed that their low complex formation ability in the endoplasmic reticulum 
      facilitates the interaction with multiple drugs.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Shirayanagi, Tomohiro
AU  - Shirayanagi T
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8675, Japan.
FAU - Kazaoka, Akira
AU  - Kazaoka A
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8675, Japan.
FAU - Watanabe, Kenji
AU  - Watanabe K
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8675, Japan.
FAU - Qu, Liang
AU  - Qu L
AD  - Department of Physical Chemistry, Graduate School of Pharmaceutical Sciences, 
      Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8675, Japan.
FAU - Sakamoto, Naoki
AU  - Sakamoto N
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8675, Japan.
FAU - Hoshino, Tyuji
AU  - Hoshino T
AD  - Department of Physical Chemistry, Graduate School of Pharmaceutical Sciences, 
      Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8675, Japan.
FAU - Ito, Kousei
AU  - Ito K
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8675, Japan.
FAU - Aoki, Shigeki
AU  - Aoki S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8675, Japan. Electronic 
      address: aokishigeki@chiba-u.jp.
LA  - eng
PT  - Journal Article
DEP - 20220511
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 33CM23913M (Carbamazepine)
SB  - IM
MH  - Carbamazepine/toxicity
MH  - *Drug Hypersensitivity/genetics
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - HLA Antigens/genetics
MH  - HLA-B Antigens/chemistry/metabolism
MH  - Humans
OTO - NOTNLM
OT  - Drug hypersensitivity
OT  - Human leukocyte antigen
OT  - Molecular dynamics simulation
OT  - beta(2)-microglobulin
EDAT- 2022/05/15 06:00
MHDA- 2022/06/07 06:00
CRDT- 2022/05/14 19:25
PHST- 2022/03/22 00:00 [received]
PHST- 2022/05/04 00:00 [revised]
PHST- 2022/05/09 00:00 [accepted]
PHST- 2022/05/15 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/05/14 19:25 [entrez]
AID - S0887-2333(22)00080-7 [pii]
AID - 10.1016/j.tiv.2022.105383 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2022 Aug;82:105383. doi: 10.1016/j.tiv.2022.105383. Epub 2022 
      May 11.