HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms
HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms
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DOI：
10.1016/j.jaci.2019.01.045
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发表时间：
2019-07-01
影响因子：
14.2
通讯作者：
Phillips, Elizabeth J.
中科院分区：
文献类型：
--
作者：
Konvinse, Katherine C.;Trubiano, Jason A.;Phillips, Elizabeth J.
工作背景：万古霉素是重度超敏反应综合征药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）的常见原因，导致显著的发病率和死亡率，通常发生在联合抗生素治疗的情况下，影响未来的治疗选择。特别是在HLA I类的变异已与严重的T细胞介导的药物不良反应，这导致了一些drugs.Objective预防性筛查策略：我们试图确定是否在HLA区域的变异与万古霉素诱导的DRESS.Methods：可能的万古霉素诱导的DRESS病例匹配1：2与耐受性对照受试者的性别，种族和年龄的基础上，使用BioVU，范德比尔特的去识别电子健康记录数据库。DRESS与HLA I类和II类等位基因携带之间的关联通过条件Logistic回归进行评估。来自BioVU的扩展样本集用于对暴露于万古霉素的患者进行时间-事件分析，其中有和没有确定的HLA风险等位基因。结果：23例受试者符合万古霉素相关DRESS的入选标准。23例患者中有19例（82.6%）携带HLA-A*32：01，而46例匹配的万古霉素耐受对照受试者中0例（0%）携带HLA-A*32：01（P = 1 x 10（-8）），BioVU人群中6.3%携带HLA-A * 32：01（n = 54，249，P = 2 x 10（-16））。在万古霉素治疗期间的HLA-A*32：01阳性组的DRESS发展的时间事件分析表明，19.2%的DRESS，并在4 weeks.Conclusions：HLA-A*32：01是强烈相关的万古霉素诱导的DRESS主要是欧洲血统的人口。HLA-A*32：01检测可以提高抗生素的安全性，有助于将万古霉素作为致病药物，并保留未来联合使用抗生素的治疗选择。
Background: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs.Objective: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS.Methods: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.Results: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 x 10(-8)) and 6.3% of the BioVU population (n = 54,249, P = 2 x 10(-16)). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks.Conclusions: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.