Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China; Department of Dermatology, Ruijin Hospital, Shanghai, China; School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Allergol Int. 2024 Oct;73(4):580-586. doi: 10.1016/j.alit.2024.03.003. Epub 2024 Apr 8.
Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs.
A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016-2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019-2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined.
The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4-8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3-63.7; P = 0.001). The in vitro BAT showed higher activation of CD63 basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P < 0.05). Only four patients (8.5%) with oxaliplatin-induced ADRs were positive for oxaliplatin-specific IgE.
This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. HLA-DRB∗12:01 is regarded as a genetic marker for oxaliplatin-induced hypersensitivity.
奥沙利铂常用于治疗胃肠道恶性肿瘤。然而，由于其潜在的药物不良反应（ADR），特别是严重的过敏性休克，其应用受到限制。目前尚无预测或预防奥沙利铂引起的 ADR 的方法。因此，我们旨在研究奥沙利铂诱导的 ADR 的遗传 HLA 易感性和免疫机制。
对 2016-2021 年我们的 ADR 报告系统中记录的 154 例奥沙利铂诱导的 ADR 患者进行回顾性分析。对 2019-2023 年 47 例奥沙利铂诱导的 ADR 患者、1100 例普通人群对照和 34 例奥沙利铂耐受对照进行 HLA 基因分型。进行体外嗜碱性粒细胞活化试验（BAT）和奥沙利铂特异性 IgE 水平测定。
我们队列中奥沙利铂诱导的 ADR 和过敏性休克的发生率分别为 7.1%和 0.15%。在 154 例患者中，67.5%出现皮疹/皮疹；26.0%无法进行奥沙利铂再挑战的患者被认为表现出奥沙利铂诱导的免疫介导的超敏反应（HRs）。遗传研究发现，与普通人群对照（敏感性=42.9%；比值比[OR] = 3.4；95%可信区间[CI] = 1.4-8.2；P = 0.008）和耐受对照（OR = 12；95% CI = 2.3-63.7；P = 0.001）相比，HLA-DRB∗12:01 等位基因与奥沙利铂诱导的 HR 相关。体外 BAT 显示，奥沙利铂诱导的 HR 患者的 CD63 嗜碱性粒细胞激活水平高于耐受对照（P<0.05）。只有 4 例（8.5%）奥沙利铂诱导的 ADR 患者奥沙利铂特异性 IgE 阳性。
本研究发现，26.0%的奥沙利铂诱导的 ADR 患者不能进行奥沙利铂再挑战。HLA-DRB∗12:01 被认为是奥沙利铂诱导过敏的遗传标志物。
