Abstract：
BACKGROUND: Population-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of patients with CU has not been reported.
OBJECTIVE: We sought to explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy.
METHODS: Plasma samples from 80 patients with CU and 82 healthy controls were collected for metabolomics quantification and bioinformatics analysis. Another independent cohort consisting of 144 patients with CU was studied to validate the findings. Bone marrow-derived mast cells and mice with IgE-induced passive cutaneous anaphylaxis were used for in vitro and in vivo experiments, respectively.
RESULTS: We observed clear metabolome differences between CU patients and healthy controls. Meanwhile, differential metabolites N6-acetyl-l-lysine, l-aspartate, maleic acid, and pyruvic acid were used to construct random forest classifiers and achieved area under receiver operating characteristic curve values greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H1 antihistamines, and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cell activation in vitro and in vivo.
CONCLUSIONS: Plasma pyruvic acid and maleic acid may be effective biomarkers for predicting disease activity, therapeutic efficacy, and prognosis for patients with CU.
OBJECTIVE: We sought to explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy.
METHODS: Plasma samples from 80 patients with CU and 82 healthy controls were collected for metabolomics quantification and bioinformatics analysis. Another independent cohort consisting of 144 patients with CU was studied to validate the findings. Bone marrow-derived mast cells and mice with IgE-induced passive cutaneous anaphylaxis were used for in vitro and in vivo experiments, respectively.
RESULTS: We observed clear metabolome differences between CU patients and healthy controls. Meanwhile, differential metabolites N6-acetyl-l-lysine, l-aspartate, maleic acid, and pyruvic acid were used to construct random forest classifiers and achieved area under receiver operating characteristic curve values greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H1 antihistamines, and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cell activation in vitro and in vivo.
CONCLUSIONS: Plasma pyruvic acid and maleic acid may be effective biomarkers for predicting disease activity, therapeutic efficacy, and prognosis for patients with CU.
摘要：
背景：基于人群的研究强调了慢性荨麻疹（CU）与代谢综合征之间的联系，在CU中发现了代谢改变。然而,根据我们的知识，一项针对大队列CU患者的全面代谢组学研究尚未报道.
目的：探讨CU诊断和治疗的潜在代谢亚型和新的代谢标志物。
方法：收集80例CU患者和82例健康对照（HC）的血浆样本进行代谢组学定量并进行生物信息学分析。另一个由144个CU患者组成的独立队列研究以验证这些发现。骨髓来源的肥大细胞（BMMC）和IgE诱导的被动皮肤过敏反应（PCA）小鼠被用于体外和体内实验，分别。
结果：我们观察到CU和HC之间明显的代谢组学差异。同时,差异代谢物N6-乙酰基-1-赖氨酸，L-天冬氨酸,用马来酸和丙酮酸分别构建随机森林分类器,并获得大于0.85的AUC，表明它们作为CU的诊断生物标志物的潜力。更重要的是,通过探索CU的潜在代谢亚型，我们发现丙酮酸和马来酸的低丰度与CU的活性显着相关，第二代H1-抗组胺药（sgAHs）疗效不佳，和短暂的无复发时间。结果在独立队列中得到验证。此外，丙酮酸或马来酸盐的补充可以在体外和体内显着减弱IgE介导的肥大细胞活化。
结论：血浆丙酮酸和马来酸的联合可能是预测疾病活动性的有效生物标志物，CU患者的治疗效果和预后。
目的：探讨CU诊断和治疗的潜在代谢亚型和新的代谢标志物。
方法：收集80例CU患者和82例健康对照（HC）的血浆样本进行代谢组学定量并进行生物信息学分析。另一个由144个CU患者组成的独立队列研究以验证这些发现。骨髓来源的肥大细胞（BMMC）和IgE诱导的被动皮肤过敏反应（PCA）小鼠被用于体外和体内实验，分别。
结果：我们观察到CU和HC之间明显的代谢组学差异。同时,差异代谢物N6-乙酰基-1-赖氨酸，L-天冬氨酸,用马来酸和丙酮酸分别构建随机森林分类器,并获得大于0.85的AUC，表明它们作为CU的诊断生物标志物的潜力。更重要的是,通过探索CU的潜在代谢亚型，我们发现丙酮酸和马来酸的低丰度与CU的活性显着相关，第二代H1-抗组胺药（sgAHs）疗效不佳，和短暂的无复发时间。结果在独立队列中得到验证。此外，丙酮酸或马来酸盐的补充可以在体外和体内显着减弱IgE介导的肥大细胞活化。
结论：血浆丙酮酸和马来酸的联合可能是预测疾病活动性的有效生物标志物，CU患者的治疗效果和预后。
