Chung Wen-Hung, Hung Shuen-Iu, Chen Yuan-Tsong
Molecular Medicine Program of Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica and School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
Curr Opin Allergy Clin Immunol. 2007 Aug;7(4):317-23. doi: 10.1097/ACI.0b013e3282370c5f.
The present article reviews the recent literature on the identification of human leukocyte antigen (HLA) alleles as major susceptible genes for drug hypersensitivity and discusses the clinical implications.
Several recent studies have reported strong genetic associations between HLA alleles and susceptibility to drug hypersensitivity. The genetic associations can be drug specific, such as HLA-B1502 being associated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), HLA-B5701 with abacavir hypersensitivity and HLA-B5801 with allopurinol-induced severe cutaneous adverse reactions. A genetic association can also be phenotype-specific, as B1502 is associated solely with carbamazepine-SJS/TEN, and not with either maculopapular eruption or hypersensitivity syndrome. Furthermore, a genetic association can also be ethnicity specific; carbamazepine-SJS/TEN associated with B*1502 is seen in south-east Asians but not in whites, which may be explained by the different allele frequencies.
The strong genetic association suggests a direct involvement of HLA in the pathogenesis of drug hypersensitivity when the HLA molecule presents an antigenic drug for T cell activation. The high sensitivity/specificity of some markers provides a plausible basis for developing tests to identify individuals at risk for drug hypersensitivity. Application of HLA-B*1502 genotyping as a screening tool before prescribing carbamazepine could be a valuable tool in preventing carbamazepine-induced SJS/TEN in south-east Asian countries.
本文综述了有关鉴定人类白细胞抗原（HLA）等位基因作为药物超敏反应主要易感基因的近期文献，并讨论了其临床意义。
多项近期研究报告了HLA等位基因与药物超敏反应易感性之间存在密切的遗传关联。这些遗传关联可能具有药物特异性，例如HLA-B1502与卡马西平诱发的史蒂文斯-约翰逊综合征及中毒性表皮坏死松解症（SJS/TEN）相关，HLA-B5701与阿巴卡韦超敏反应相关，以及HLA-B5801与别嘌醇诱发的严重皮肤不良反应相关。遗传关联也可能具有表型特异性，因为B1502仅与卡马西平-SJS/TEN相关，而与斑丘疹或超敏综合征均无关。此外，遗传关联还可能具有种族特异性；与B*1502相关的卡马西平-SJS/TEN在东南亚人中可见，而在白人中未见，这可能由不同的等位基因频率来解释。
这种密切的遗传关联表明，当HLA分子呈递抗原性药物以激活T细胞时，HLA直接参与了药物超敏反应的发病机制。某些标志物的高敏感性/特异性为开发用于识别药物超敏反应风险个体的检测方法提供了合理依据。在东南亚国家，在开具卡马西平处方前应用HLA-B*1502基因分型作为筛查工具，可能是预防卡马西平诱发SJS/TEN的一项有价值的工具。
