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第I类HLA单基因与奥西默提尼布诱导过敏症的风险增加有关

Chun-Bing Chen¹, Chuang-Wei Wang², Chun-Wei Lu³

¹Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, and Keelung, Taiwan; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; School of Medicine, National Tsing Hua University, Hsinchu, Taiwan.

The journal of allergy and clinical immunology. In practice

|November 6, 2024

概括

人类白细胞抗原 (HLA) -B51:02与服用奥西默提尼布的患者的严重过敏反应密切相关,包括史蒂文斯-约翰逊综合征/有毒表皮解. 对HLA-B51:02的基因查可以帮助预防这些危险的不良事件.

科学领域:

药物基因组学药物基因组学
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

奥西默提尼布是一种第三代表皮生长因子受体-铁氨酸激酶抑制剂 (EGFR-TKI),对肺癌有效.
严重的过敏反应,如史蒂文斯-约翰逊综合征 (SJS) /有毒表皮解体 (TEN),在接受奥西默蒂尼布治疗的亚洲人群中很常见,限制了其使用.

研究的目的:

调查基因人类白细胞抗原 (HLA) 倾向和免疫病理机制,是奥西默提尼布诱导过敏的基础.
为了确定与不同严重程度的 osimertinib 过敏相关的特定 HLA 基因.

主要方法:

人类白细胞抗原 (HLA) 基因组的基因型定型在17名患有奥西默蒂尼布诱导过敏症的患者 (7例严重SJS/TEN,10例轻微的斑点斑膜外血症),98名耐受奥西默蒂尼布的受试者和2,123名一般人群对照.
进行药物诱导的淋巴细胞激活测试和表面等离子体共振测试,以评估免疫反应和药物蛋白相互作用.

主要成果:

HLA-B51:02与奥西默提尼布诱导的SJS/TEN显著相关 (83.3%的患者与3.3%的对照组;P<10-6).
HLA-B51:01和HLA-A24:02与轻度的斑点斑点外血有关.
升高的花素水平和体外阳性淋巴细胞激活证实了SJS/TEN免疫病理学. HLA-B51:02显示出与 osimertinib 的结合亲和力更高.

结论:

在亚洲人群中,HLA-B51:02是严重的奥西默提尼布诱导过敏症 (SJS/TEN) 的强烈遗传标志物.
预防性查HLA-B51:02可能会减少对奥西默提尼布的严重不良反应的发生率.
对奥西默蒂尼布过敏的患者可能会耐受其他EGFR-TKIs,而HLA-B51:02对奥西默蒂尼布具有特定的结合亲和力.

关键词:

在HLA-B51:02中.过敏症是一种过敏症.奥西默蒂尼布 (Osimertinib) 是一种药物.史蒂文斯 - 约翰逊综合征有毒的表皮死亡解剖.

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