Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria

Xingxing Jian; Guixue Hou; Liqiao Li; Zhuo Diao; Yingfang Wu; Jiayi Wang; Lu Xie; Cong Peng; Liang Lin; Jie Li

doi:10.1016/j.jaci.2024.01.032

Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria

J Allergy Clin Immunol. 2024 Apr 9:S0091-6749(24)00336-1. doi: 10.1016/j.jaci.2024.01.032. Online ahead of print.

Authors

Xingxing Jian¹, Guixue Hou², Liqiao Li³, Zhuo Diao², Yingfang Wu⁴, Jiayi Wang⁴, Lu Xie⁵, Cong Peng⁶, Liang Lin⁷, Jie Li⁸

Affiliations

¹ Department of Dermatology (Dermatology Hospital), Xiangya Hospital, Central South University, Changsha, China; Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
² BGI Group, Shenzhen, China.
³ Department of Dermatology (Dermatology Hospital), Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China; Department of Dermatology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
⁴ Department of Dermatology (Dermatology Hospital), Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China.
⁵ Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁶ Department of Dermatology (Dermatology Hospital), Xiangya Hospital, Central South University, Changsha, China; Furong Laboratory, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China.
⁷ BGI Group, Shenzhen, China. Electronic address: linl@genomics.cn.
⁸ Department of Dermatology (Dermatology Hospital), Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China. Electronic address: xylijie@csu.edu.cn.

PMID: 38599289
DOI: 10.1016/j.jaci.2024.01.032

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.

Keywords: CU; Chronic urticaria; maleate; metabolic subtypes; metabolomics signatures; pyruvate.