青少年及成人特应性皮炎患者血浆氨基酸代谢水平分析

Analysis of plasma amino acid profiles in adolescents and adults with atopic dermatitis

目的通过靶向代谢组学分析青少年和成人特应性皮炎(AD)患者血浆氨基酸代谢变化,并进一步分析总IgE升高与正常的AD患者间以及伴与不伴过敏性鼻炎的AD患者间血浆氨基酸代谢的差异,从代谢途径探讨AD的发病机制。方法2021年12月至2022年6月在锦州医科大学附属第一医院皮肤科确诊的>12岁AD患者40例作为研究对象,同时30例健康体检者作为对照组。采用高效液相-质谱技术检测血浆样本中的代谢物质,利用主成分分析法(PCA)及正交偏最小二乘-判别分析法(OPLS-DA)分析数据,选取OPLS-DA模型中第一主成分的变量权重值(VIP)>1及t检验中P<0.05作为差异代谢物,通过MetaboAnalyst 5.0软件分析可能存在的异常代谢通路,影响值(impact)>0.1及P<0.05时认为是差异代谢通路。结果PCA得分图和OPLS-DA模型分析显示,各组间代谢物区分良好,筛选出差异代谢物及代谢通路:比较AD组与对照组,发现12个差异代谢物及8条差异代谢通路,其中差异代谢物如精氨酸[代谢水平:(28.257±11.517)μmol/L比(21.038±8.500)μmol/L,VIP=1.32,P=0.001]、鸟氨酸[(47.597±18.158)μmol/L比(36.937±5.813)μmol/L,VIP=1.26,P<0.001]和组氨酸[(78.322±14.971)μmol/L比(100.694±32.419)μmol/L,VIP=1.33,P<0.001],差异代谢通路如精氨酸生物合成(impact=0.482,P<0.001)及组氨酸代谢(impact=0.221,P<0.001);比较IgE升高的AD组与IgE正常的AD组,发现5个差异代谢物和3条差异代谢通路,其中差异代谢物如赖氨酸[(313.998±61.252)μmol/L比(285.330±58.388)μmol/L,VIP=2.25,P<0.001]和甘氨酸[(200.807±53.320)μmol/L比(187.056±50.941)μmol/L,VIP=1.40,P=0.014],差异代谢通路如乙醛酸盐和二羧酸盐代谢通路(impact=0.105,P=0.001);比较伴与不伴过敏性鼻炎AD组,发现6个差异代谢物和3条差异代谢通路,其中差异代谢通路有精氨酸生物合成(impact=0.116,P<0.001)。结论青少年及成人AD患者血浆氨基酸代谢水平与健康对照有差异,精氨酸、鸟氨酸代谢水平升高及组氨酸代谢水平降低可能与AD发病相关;赖氨酸、甘氨酸代谢水平升高与伴IgE升高的AD相关;精氨酸生物合成代谢通路与伴过敏性鼻炎的AD有关。

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±11.517μmol/L vs.21.038±8.500μmol/L,VIP=1.32,P=0.001),ornithine(47.597±18.158μmol/L vs.36.937±5.813μmol/L,VIP=1.26,P<0.001)and histidine(78.322±14.971μmol/L vs.100.694±32.419μmol/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±61.252μmol/L vs.285.330±58.388μmol/L,VIP=2.25,P<0.001)and glycine(200.807±53.320μmol/L vs.187.056±50.941μmol/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.