关键词: 皮炎, 特应性, 青少年, 成年人, 代谢组学, 氨基酸类, 免疫球蛋白E, 过敏性鼻炎

Abstract: 【Abstract】 Objective To analyze changes in plasma amino acid profiles in adolescents and adults with atopic dermatitis （AD） by targeted metabolomics, to further analyze differences in plasma amino acid profiles between AD patients with elevated total IgE levels and those with normal total IgE levels, as well as between AD patients with and without allergic rhinitis, and to explore the pathogenesis of AD from the perspective of metabolic pathways. Methods From December 2021 to June 2022, 40 AD patients aged > 12 years were collected as research subjects from the Department of Dermatology, the First Affiliated Hospital of Jinzhou Medical University, and 30 healthy checkup examinees served as a control group at the same time. Plasma samples were obtained from the subjects, and high-performance liquid chromatography-mass spectrometry was performed to detect levels of metabolites in the plasma samples. Principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were carried out to analyze data and screen out differential metabolites with the variable weight value （VIP） of the first principal component being > 1 in the OPLS-DA model and the P value being < 0.05 in the t test. Possible abnormal metabolic pathways were analyzed using MetaboAnalyst 5.0 software, and differential metabolic pathways were defined as those with an impact value of > 0.1 and a P value of < 0.05. Results PCA and OPLS-DA model analysis showed that metabolites were well differentiated among the groups, and differential metabolites and metabolic pathways were screened out. Concretely speaking, 12 differential metabolites and 8 differential metabolic pathways were identified by comparing the AD group with the control group, among which differential metabolites included arginine （metabolic levels: 28.257 ± 11.517 μmol/L vs. 21.038 ± 8.500 μmol/L, VIP = 1.32, P = 0.001）, ornithine （47.597 ± 18.158 μmol/L vs. 36.937 ± 5.813 μmol/L, VIP = 1.26, P < 0.001） and histidine （78.322 ± 14.971 μmol/L vs. 100.694 ± 32.419 μmol/L, VIP = 1.33, P < 0.001）, and differential metabolic pathways included arginine biosynthesis （impact = 0.482, P < 0.001） and histidine metabolism （impact = 0.221, P < 0.001）. Comparisons between the AD group with elevated IgE levels and those with normal IgE levels showed 5 differential metabolites and 3 differential metabolic pathways, among which differential metabolites included lysine （313.998 ± 61.252 μmol/L vs. 285.330 ± 58.388 μmol/L, VIP = 2.25, P < 0.001） and glycine （200.807 ± 53.320 μmol/L vs. 187.056 ± 50.941 μmol/L, VIP = 1.40, P = 0.014）, and differential metabolic pathways included the glyoxylate and dicarboxylate metabolic pathway （impact = 0.105, P = 0.001）; by comparing the AD group with and without allergic rhinitis, 6 differential metabolites and 3 differential metabolic pathways were identified, among which the arginine biosynthesis metabolic pathway was highlighted （impact = 0.116, P < 0.001）. Conclusion The plasma amino acid metabolites in adolescents and adults with AD were different from those in healthy controls, and elevated plasma levels of arginine and ornithine and decreased plasma level of histidine may be involved in the pathogenesis of AD; increased plasma levels of lysine and glycine were associated with AD with elevated IgE levels; the arginine biosynthetic metabolic pathway was related to AD complicated by allergic rhinitis.

Key words: Dermatitis, atopic, Adolescent, Adult, Metabolomics, Amino acids, Immunoglobulin E, Allergic rhinitis