School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, P. R. China.
Shanxi Key Laboratory of Forensic Medicine, Shanxi, 030600, P. R. China.
Sci Rep. 2024 Oct 9;14(1):23534. doi: 10.1038/s41598-024-74623-x.
Immunoglobulin E (IgE)-mediated immediate hypersensitivity reactions are the most concerning adverse events after penicillin antibiotics (PENs) administration because of their rapid progression and potential for fatal outcome. However, the diagnosis of allergic death is a forensic challenge because it mainly depends on nonspecific characteristic morphological changes, as well as exclusion and circumstantial evidence. In this study, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) was used to screen potential forensic biomarkers of fatal anaphylactic shock induced by four PENs (benzylpenicillin (BP), amoxicillin (AMX), oxacillin (OXA), and mezlocillin (MEZ)), and analyzed the metabolites, metabolic pathway and the mechanism which were closely related to the allergic reactions. The metabolomics results discovered that a total of 24 different metabolites in all four anaphylactic death (AD) groups, seven of which were common metabolites. A biomarker model consisting of six common metabolites (linoleic acid, prostaglandin D2, lysophosphatidylcholine (18:0), N-acetylhistamine, citric acid and indolelactic acid) AUC value of Receiver Operating Characteristic (ROC) curve was 0.978. Metabolism pathway analysis revealed that the pathogenesis of PENs-induced AD is closely related to linoleic acid metabolism. Our results revealed that the metabolomic profiling has potential in PENs-induced AD post-mortem diagnosis and metabolic mechanism investigations.
免疫球蛋白 E（IgE）介导的即刻超敏反应是青霉素类抗生素（PENs）给药后最令人担忧的不良事件，因为它们进展迅速，可能导致致命后果。然而，过敏死亡的诊断是法医学上的一个挑战，因为它主要取决于非特异性特征形态变化，以及排除和环境证据。在这项研究中，我们采用基于液相色谱-质谱（LC-MS）的非靶向代谢组学方法筛选了四种 PENs（苄青霉素（BP）、阿莫西林（AMX）、苯唑西林（OXA）和美洛西林（MEZ））引起致命过敏性休克的潜在法医生物标志物，并分析了与过敏反应密切相关的代谢物、代谢途径和机制。代谢组学结果发现，所有四个过敏性死亡（AD）组中共有 24 种不同的代谢物，其中 7 种是共同代谢物。一个由六种共同代谢物（亚油酸、前列腺素 D2、溶血磷脂酰胆碱（18:0）、N-乙酰组氨酸、柠檬酸和吲哚乳酸）组成的生物标志物模型的 ROC 曲线 AUC 值为 0.978。代谢途径分析表明，PENs 诱导的 AD 发病机制与亚油酸代谢密切相关。我们的研究结果表明，代谢组学分析具有在 PENs 诱导的 AD 死后诊断和代谢机制研究中的应用潜力。
