Delayed‐type, T cell–mediated, drug hypersensitivity reactions are a serious unwanted manifestation of drug exposure that develops in a small percentage of the human population. Drugs and drug metabolites are known to interact directly and indirectly (through irreversible protein binding and processing to the derived adducts) with HLA proteins that present the drug‐peptide complex to T cells. Multiple forms of drug hypersensitivity are strongly linked to expression of a single HLA allele, and there is increasing evidence that drugs and peptides interact selectively with the protein encoded by the HLA allele. Despite this, many individuals expressing HLA risk alleles do not develop hypersensitivity when exposed to culprit drugs suggesting a nonlinear, multifactorial relationship in which HLA risk alleles are one factor. This has prompted a search for additional susceptibility factors. Herein, we argue that immune regulatory pathways are one key determinant of susceptibility. As expression and activity of these pathways are influenced by disease, environmental and patient factors, it is currently impossible to predict whether drug exposure will result in a health benefit, hypersensitivity or both. Thus, a concerted effort is required to investigate how immune dysregulation influences susceptibility towards drug hypersensitivity.

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免疫失调增加迟发型药物超敏反应的发生率

延迟型、T 细胞介导的药物超敏反应是在一小部分人群中发生的药物暴露的严重不良表现。已知药物和药物代谢物与将药物肽复合物呈递给 T 细胞的 HLA 蛋白直接和间接相互作用（通过不可逆的蛋白质结合和加工衍生的加合物）。多种形式的药物超敏反应与单个 HLA 等位基因的表达密切相关，越来越多的证据表明药物和肽选择性地与 HLA 等位基因编码的蛋白质相互作用。尽管如此，许多表达 HLA 风险等位基因的个体在暴露于罪犯药物时不会产生超敏反应，这表明存在非线性、多因素关系，其中 HLA 风险等位基因是一个因素。这促使人们寻找其他易感因素。在此，我们认为免疫调节途径是易感性的关键决定因素之一。由于这些途径的表达和活性受疾病、环境和患者因素的影响，目前无法预测药物暴露是否会导致健康益处、超敏反应或两者兼而有之。因此，需要共同努力研究免疫失调如何影响对药物超敏反应的易感性。超敏反应或两者兼而有之。因此，需要共同努力研究免疫失调如何影响对药物超敏反应的易感性。超敏反应或两者兼而有之。因此，需要共同努力研究免疫失调如何影响对药物超敏反应的易感性。