Genome-wide DNA methylation profiling identifies epigenetic signatures of β-lactams induced fatal anaphylactic shock

Drug hypersensitivity is one of the most frequent causes of anaphylaxis in adults, of which antibiotics are the most common culprits, particularly β-lactams induced anaphylactic shock deaths. We provided the genome wide DNA methylation profiling study of PBMC from 14 individuals peripheral venous blood samples. Illumina Infinium Human Methylation EPIC BeadChip was used. Among the 14 individuals, 8 patients were died from β-lactams induced anaphylactic shock, 6 healthy individuals were controls. Inclusion criteria for the β-lactams induced anaphylactic shock as follows: ①A clear history of β-lactams transfusion or components of β-lactams detected from blood (or skin of suspicious infusion site); ②Shock symptoms occurred after infusion of β-lactams and died within a short period of time; ③The immunohistochemical results of throat, lung and gastrointestinal tissues showed that tryptase or chymase were mostly positive expression; ④ Excluding other causes (disease, poisoning) of death; ⑤ No decay occurred in the corpse.Inclusion criteria for controls as follows: ① Healthy, no previous common underlying diseases and no history of genetic disease; ② No history of allergies to drugs, food, pollen and so on; ③Skin prick test (SPT) is negative, allergen-specific IgE (sIgE)< 100IU/mL; the skin test results of β-lactam drugs were negative.药物超敏反应是成人发生严重过敏反应最常见的诱因之一，其中抗生素为最常见的致病原，尤以β-内酰胺类（β-lactams）诱导的过敏性休克致死案例最为突出。本研究针对14名个体外周静脉血样本中的外周血单个核细胞（peripheral blood mononuclear cell, PBMC）开展了全基因组DNA甲基化谱分析，实验采用Illumina Infinium人类甲基化EPIC微珠芯片（Illumina Infinium Human Methylation EPIC BeadChip）进行检测。14名受试者中，8例为β-内酰胺类药物诱导的过敏性休克致死患者，6例健康个体作为对照。 β-内酰胺类诱导过敏性休克患者的纳入标准如下：①明确存在β-内酰胺类药物输注史，或血液、可疑输注部位皮肤中检测到β-内酰胺类药物成分；②输注β-内酰胺类药物后出现休克症状，并于短时间内死亡；③咽喉、肺及胃肠道组织的免疫组化检测结果显示，类胰蛋白酶（tryptase）或糜蛋白酶（chymase）多呈阳性表达；④排除其他死因（疾病、中毒）；⑤尸体未出现腐败现象。 对照个体的纳入标准如下：①身体健康，无常见基础疾病及遗传病史；②无药物、食物、花粉等过敏原过敏史；③皮肤点刺试验（skin prick test, SPT）结果为阴性，过敏原特异性IgE（allergen-specific IgE, sIgE）水平＜100IU/mL，且β-内酰胺类药物的皮肤试验结果为阴性。