Phillips Elizabeth J, Mallal Simon A
Royal Perth Hospital and PathWest, Department of Clinical Immunology and Immunogenetics, Western Australia, Australia.
Curr Opin Mol Ther. 2009 Jun;11(3):231-42.
The discovery of new associations between drug toxicities and specific HLA alleles has been facilitated by the use of DNA-based molecular techniques and the introduction of higher-resolution HLA typing, which have replaced serological typing in this field of study. Drug toxicity/HLA associations have been best documented for immunologically mediated reactions, such as drug hypersensitivity reactions associated with the use of abacavir, and severe cutaneous adverse drug reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis induced by carbamazepine and allopurinol use, respectively. The implementation of HLA-B5701 screening for the prevention of abacavir hypersensitivity syndrome (ABC HSR) has provided a model approach that can be applied to the screening of other drugs. High-level clinical evidence supporting HLA-B5701 screening for ABC HSR has converged with experimental findings characterizing the CD8+T-cell HLA-B5701-restricted immune response triggered by abacavir. This has been followed by the successful development of simplified inexpensive and quality-assured laboratory tests for HLA-B5701 and ongoing quality assurance programs, resulting in a paradigm both for the implementation of HLA-B*5701 screening for HIV providers as well as for the broader successful implementation of pharmacogenetic screening in the clinic.
基于DNA的分子技术的应用以及更高分辨率的HLA分型方法的引入，推动了药物毒性与特定HLA等位基因之间新关联的发现，这些技术已在该研究领域取代了血清学分型。药物毒性/HLA关联在免疫介导的反应中记录最为详尽，例如与阿巴卡韦使用相关的药物超敏反应，以及严重的皮肤药物不良反应，如分别由卡马西平和别嘌醇使用引起的史蒂文斯 - 约翰逊综合征和中毒性表皮坏死松解症。实施HLA - B5701筛查以预防阿巴卡韦超敏综合征（ABC HSR）提供了一种可应用于其他药物筛查的模式方法。支持ABC HSR进行HLA - B5701筛查的高水平临床证据与表征由阿巴卡韦触发的CD8 + T细胞HLA - B5701限制性免疫反应的实验结果相吻合。随后成功开发了用于HLA - B5701的简化、廉价且质量有保证的实验室检测方法以及持续的质量保证计划，这为HIV治疗提供者实施HLA - B*5701筛查以及在临床中更广泛地成功实施药物遗传学筛查树立了典范。
