Genotyping for severe drug hypersensitivity.

Genotyping for severe drug hypersensitivity.
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DOI:
10.1007/s11882-013-0418-0
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发表时间:
2014-03
影响因子:
5.5
通讯作者:
Phillips, Elizabeth
Phillips, Elizabeth
中科院分区:
医学2区
文献类型:
--
作者:
Karlin, Eric;Phillips, Elizabeth

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在过去的十年中,我们对严重免疫介导的药物不良反应的免疫发病机制和药物基因组学的理解取得了重大进展。这些t细胞介导的药物不良反应,如Stevens-Johnson综合征/中毒性表皮坏死松解症(SJS/TEN)、药物性肝病(DILI)和其他药物超敏综合征,最近被证明是通过与各种I类和II类HLA等位基因的相互作用介导的。主要的例子包括东南亚人群中HLA-B*15:02和卡马西平诱导的SJS/TEN的关联,以及HLA-B*57:01和阿巴卡韦超敏反应的关联。HLA-B*57:01筛选预防阿巴卡韦超敏反应是一个成功的从药物基因组学发现到广泛临床应用的转化路线图。最终,我们对药物与MHC之间相互作用的进一步了解可以用于药物设计和推动临床前毒性项目,以提高药物安全性。
Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety.
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