JCI Insight. 2022 Apr 8;7(7):e156669. doi: 10.1172/jci.insight.156669.
BackgroundThere is a need to support the diagnosis of anaphylaxis by objective markers. miRNAs are promising noncoding RNA species that may serve as serological biomarkers, but their use in diagnosing anaphylaxis has not been systematically studied to our knowledge. We aimed to comprehensively investigate serum biomarker profiles (proteins, lipids, and miRNAs) to support the diagnosis of anaphylaxis.MethodsAdult patients admitted to the emergency room with a diagnosis of anaphylaxis (<3 hours) were included. Blood samples were taken upon emergency room arrival and 1 month later.ResultsNext-generation sequencing of 18 samples (6 patients with anaphylaxis in both acute and nonacute condition, for 12 total samples, and 6 healthy controls) identified hsa-miR-451a to be elevated during anaphylaxis, which was verified by quantitative real-time PCR in the remaining cohort. The random forest classifier enabled us to classify anaphylaxis with high accuracy using a composite model. We identified tryptase, 9α,11β-PGF2, apolipoprotein A1, and hsa-miR-451a as serological biomarkers of anaphylaxis. These predictors qualified as serological biomarkers individually but performed better in combination.ConclusionUnexpectedly, hsa-miR-451a was identified as the most relevant biomarker in our data set. We were also able to distinguish between patients with a history of anaphylaxis and healthy individuals with higher accuracy than any other available model. Future studies will need to verify miRNA biomarker utility in real-life clinical settings.FundingThis work is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) as part of the clinical research unit (CRU339): Food Allergy and Tolerance (FOOD@) (project number 409525714) and a grant to MW (Wo541-16-2, project number 264921598), as well as by FOOD@ project numbers 428094283 and 428447634.
需要通过客观标志物来支持过敏反应的诊断。miRNAs 是一种很有前途的非编码 RNA 物种,它们可能作为血清生物标志物,但据我们所知,它们在过敏反应诊断中的应用尚未得到系统研究。我们旨在全面研究血清生物标志物谱(蛋白质、脂质和 miRNAs),以支持过敏反应的诊断。
纳入因过敏反应(<3 小时)而被收入急诊室的成年患者。在急诊室到达时和 1 个月后采集血样。
对 18 个样本(6 名急性和非急性过敏患者,共 12 个样本,6 名健康对照)进行下一代测序,发现 hsa-miR-451a 在过敏反应时升高,在其余队列中通过定量实时 PCR 进行验证。随机森林分类器使我们能够使用复合模型以高精度对过敏反应进行分类。我们确定了类胰蛋白酶、9α,11β-PGF2、载脂蛋白 A1 和 hsa-miR-451a 作为过敏反应的血清生物标志物。这些预测因子作为单独的血清生物标志物具有特异性,但在组合使用时效果更好。
出乎意料的是,hsa-miR-451a 被确定为我们数据集最相关的生物标志物。与任何其他可用模型相比,我们还能够以更高的准确性区分有过敏反应病史的患者和健康个体。未来的研究将需要验证 miRNA 生物标志物在现实临床环境中的实用性。
这项工作由德国研究基金会(DFG,德国研究基金会)作为临床研究单位(CRU339)的一部分资助:食物过敏和耐受(FOOD@)(项目编号 409525714)和一项授予 MW 的资助(Wo541-16-2,项目编号 264921598),以及由 FOOD@ 项目编号 428094283 和 428447634 资助。