Riga Stradiņš University, Riga, Latvia.
Institute of Biomaterials and Bioengineering, Faculty of Natural Sciences and Technology, Riga Technical University, Riga, Latvia.
Front Immunol. 2024 Apr 25;15:1324671. doi: 10.3389/fimmu.2024.1324671. eCollection 2024.
Hereditary angioedema (HAE) is a rare, life-threatening autosomal dominant genetic disorder caused by a deficient and/or dysfunctional C1 esterase inhibitor (C1-INH) (type 1 and type 2) leading to recurrent episodes of edema. This study aims to explore HAE patients' metabolomic profiles and identify novel potential diagnostic biomarkers for HAE. The study also examined distinguishing HAE from idiopathic angioedema (AE).
Blood plasma samples from 10 HAE (types 1/2) patients, 15 patients with idiopathic AE, and 20 healthy controls were collected in Latvia and analyzed using LC-MS based targeted metabolomics workflow. T-test and fold change calculation were used to identify metabolites with significant differences between diseases and control groups. ROC analysis was performed to evaluate metabolite based classification model.
A total of 33 metabolites were detected and quantified. The results showed that isovalerylcarnitine, cystine, and hydroxyproline were the most significantly altered metabolites between the disease and control groups. Aspartic acid was identified as a significant metabolite that could differentiate between HAE and idiopathic AE. The mathematical combination of metabolites (hydroxyproline * cystine)/(creatinine * isovalerylcarnitine) was identified as the diagnosis signature for HAE. Furthermore, glycine/asparagine ratio could differentiate between HAE and idiopathic AE.
Our study identified isovalerylcarnitine, cystine, and hydroxyproline as potential biomarkers for HAE diagnosis. Identifying new biomarkers may offer enhanced prospects for accurate, timely, and economical diagnosis of HAE, as well as tailored treatment selection for optimal patient care.
遗传性血管性水肿（HAE）是一种罕见的、危及生命的常染色体显性遗传性疾病，由 C1 酯酶抑制剂（C1-INH）（1 型和 2 型）缺陷和/或功能障碍引起，导致反复出现水肿发作。本研究旨在探索 HAE 患者的代谢组学特征，并确定 HAE 的新的潜在诊断生物标志物。该研究还检查了将 HAE 与特发性血管性水肿（AE）区分开来的方法。
在拉脱维亚收集了 10 名 HAE（1/2 型）患者、15 名特发性 AE 患者和 20 名健康对照者的血液血浆样本，并使用基于 LC-MS 的靶向代谢组学工作流程进行分析。使用 t 检验和倍数变化计算来鉴定疾病组和对照组之间具有显著差异的代谢物。进行 ROC 分析以评估基于代谢物的分类模型。
共检测到并定量了 33 种代谢物。结果表明，异戊酰肉碱、胱氨酸和羟脯氨酸是疾病组和对照组之间变化最显著的代谢物。天冬氨酸被鉴定为可区分 HAE 和特发性 AE 的显著代谢物。代谢物（羟脯氨酸胱氨酸）/（肌酐异戊酰肉碱）的数学组合被鉴定为 HAE 的诊断特征。此外，甘氨酸/天冬酰胺比可以区分 HAE 和特发性 AE。
我们的研究确定了异戊酰肉碱、胱氨酸和羟脯氨酸作为 HAE 诊断的潜在生物标志物。识别新的生物标志物可能为 HAE 的准确、及时和经济的诊断以及为优化患者护理的个体化治疗选择提供更好的前景。
