Practical Implementation of Genetics: New Concepts in Immunogenomics to Predict, Prevent, and Diagnose Drug Hypersensitivity.
Practical Implementation of Genetics: New Concepts in Immunogenomics to Predict, Prevent, and Diagnose Drug Hypersensitivity.
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遗传学的实际应用：免疫基因组学中预测、预防和诊断药物超敏反应的新概念。
DOI：
10.1016/j.jaip.2022.04.027
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发表时间：
2022-07
影响因子：
9.4
通讯作者：
Gibson, Andrew
中科院分区：
文献类型：
--
作者：
Deshpande, Pooja;Li, Yueran;Thorne, Michael;Palubinsky, Amy M.;Phillips, Elizabeth J.;Gibson, Andrew
关键词：
延迟性药物超敏反应是CD8+ t细胞介导的反应，与高达50%的死亡率相关。已知人类白细胞抗原（HLA）等位基因易患疾病，对药物、反应和患者种族具有特异性，建议在治疗前进行筛选，以确定和预防高危患者使用药物。然而，不完整的预测值暗示了其他hla强加的风险因素，并且许多已确定的hla风险等位基因的低携带加上基于序列的分型的高成本限制了跨药物和医疗保健系统筛查的类似推荐的经济可行性。为了减轻这种情况，正在开发一种不断扩大的低成本基于聚合酶链反应的筛查方法，并且正在发现hla强加的风险因素。这些包括代谢和内质网氨基肽酶的多态性变异，对多等位基因筛选具有更高的预测性，免疫检查点抑制剂的调节，使人类疾病的去耐受性动物模型成为可能，以及免疫显性t细胞受体（TCR）在克隆扩增的CD8+ t细胞上。对于后者，hla风险受限的TCR提供了免疫基因组策略和单个患者的样本，以确定服务不足的少数人群中新的hla风险关联，组织相关效应生物标志物，用于早期诊断和治疗，以及hla -TCR呈现的免疫原性结构，以帮助未来的药物开发。
Delayed drug hypersensitivities are CD8+ T-cell mediated reactions associated with up to 50% mortality. Human leukocyte antigen (HLA) alleles are known to predispose disease, specific to drug, reaction, and patient ethnicity, with pre-treatment screening recommended for a handful of the strongest associations to identify and prevent drug use in high-risk patients. However, an incomplete predictive value implicates other HLA-imposed risk factors, and low carriage of many identified HLA-risk alleles combined with the high cost of sequence-based typing has limited economic viability for similar recommendation of screening across drugs and healthcare systems. To mitigate, an expanding armoury of low-cost polymerase chain reaction-based screens is being developed, and HLA-imposed risk factors are being discovered. These include polymorphic variants of metabolic and endoplasmic reticulum aminopeptidase enzymes, towards multi-allelic screening with increased predictivity, regulation by immune checkpoint inhibitors, enabling de-tolerised animal models of human disease, and immunodominant T-cell receptors (TCR) on clonally expanded CD8+ T-cells. For the latter, HLA-risk restricted TCR provides immunogenomic strategies and samples from a single patient to identify novel HLA-risk associations in underserved minority populations, tissue-relevant effector biomarkers towards earlier diagnosis and treatment, and HLA-TCR-presented immunogenic structures to aid future drug development.
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影响因子：
56.9
作者：
Arstila, TP;Casrouge, A;Kourilsky, P
通讯作者：
Kourilsky, P
影响因子：
2.7
作者：
Dinh Van Nguyen;Vidal, Christopher;Fernando, Suran L.
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Fernando, Suran L.
影响因子：
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作者：
Fang, Hua;Xu, Xiequn;Moreno, Tanya A.
通讯作者：
Moreno, Tanya A.
DOI：
10.1097/00008571-199712000-00011
发表时间：
1997-12-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Delomenie, C;MathelierFusade, P;Dupret, JM
通讯作者：
Dupret, JM
影响因子：
7.3
作者：
Chronister WD;Crinklaw A;Mahajan S;Vita R;Koşaloğlu-Yalçın Z;Yan Z;Greenbaum JA;Jessen LE;Nielsen M;Christley S;Cowell LG;Sette A;Peters B
通讯作者：
Peters B