Negrini Simone, Becquemont Laurent
Department of internal medicine, clinical immunology unit, centre of excellence for biomedical research, university of Genoa, 16132 Genoa, Italy.
Pharmacology department, faculty of medicine Paris-Sud, UMR 1184, CEA, DSV/iMETI, division of immuno-virology, IDMIT, Inserm center for immunology of viral infections and autoimmune diseases, hôpital Bicêtre, university Paris Sud, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
Therapie. 2017 Apr;72(2):231-243. doi: 10.1016/j.therap.2016.12.009. Epub 2017 Jan 3.
Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity. Most notable examples include human leukocyte antigen (HLA)-B57:01 allele and abacavir hypersensitivity syndrome or HLA-B15:02 and HLA-B*58:01 alleles related to severe cutaneous reactions induced by carbamazepine and allopurinol, respectively. This review aims to explore our current understanding in the field of pharmacogenomics of HLA-associated drug hypersensitivities and its translation into clinical practice for predicting adverse drug reactions.
药物不良反应是发病和死亡的重要原因,也是医疗保健系统的重大负担。其中一些反应是由免疫介导的(超敏反应),临床上可分为两类:速发型反应(与IgE相关)和迟发型反应(T细胞介导)。迟发型超敏反应包括全身性综合征和器官特异性毒性,可由多种化学性质不同的药物引发。最近的研究表明,人类白细胞抗原等位基因与迟发型药物超敏反应易感性之间存在很强的遗传关联。最显著的例子包括人类白细胞抗原(HLA)-B57:01等位基因与阿巴卡韦超敏综合征,或分别与卡马西平和别嘌醇引起的严重皮肤反应相关的HLA-B15:02和HLA-B*58:01等位基因。本综述旨在探讨我们目前对HLA相关药物超敏反应药物基因组学领域的理解,以及将其转化为预测药物不良反应的临床实践。