論文 - 詳細
| RRC ID | 74468 |
|---|---|
| 著者 | Shirayanagi T, Kazaoka A, Watanabe K, Qu L, Sakamoto N, Hoshino T, Ito K, Aoki S. |
| タイトル | Weak complex formation of adverse drug reaction-associated HLAB57, B58, and B15 molecules. |
| ジャーナル | Toxicol In Vitro |
| Abstract |
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 β2-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 β2-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. |
| 巻・号 | 82 |
| ページ | 105383 |
| 公開日 | 2022-8-1 |
| DOI | 10.1016/j.tiv.2022.105383 |
| PII | S0887-2333(22)00080-7 |
| PMID | 35568130 |
| MeSH | Carbamazepine / toxicity Drug Hypersensitivity* / genetics Drug-Related Side Effects and Adverse Reactions* HLA Antigens / genetics HLA-B Antigens / chemistry HLA-B Antigens / metabolism Humans |
| IF | 2.959 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa |