Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China.
Exp Dermatol. 2024 May;33(5):e15103. doi: 10.1111/exd.15103.
Erythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. Metabolomics analysis can provide global information on disease pathophysiology, candidate biomarkers, and potential intervention strategies. To gain a better understanding of the mechanisms of EP and explore the serum metabolic signature of EP, we conducted an untargeted metabolomics analysis from 20 EP patients and 20 healthy controls. Furthermore, targeted metabolomics for focused metabolites were identified in the serum samples of 30 EP patients and 30 psoriasis vulgaris (PsV) patients. In the untargeted analysis, a total of 2992 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed significant difference between groups. After screening, 98 metabolites were found to be significantly dysregulated in EP, including 67 down-regulated and 31 up-regulated. EP patients had lower levels of L-tryptophan, L-isoleucine, retinol, lysophosphatidylcholine (LPC), and higher levels of betaine and uric acid. KEGG analysis showed differential metabolites were enriched in amino acid metabolism and glycerophospholipid metabolism. The targeted metabolomics showed lower L-tryptophan in EP than PsV with significant difference and L-tryptophan levels were negatively correlated with the PASI scores. The serum metabolic signature of EP was discovered. Amino acid and glycerophospholipid metabolism were dysregulated in EP. The metabolite differences provide clues for pathogenesis of EP and they may provide insights for therapeutic interventions.
红皮病型银屑病(EP)是一种罕见且危及生命的疾病,其发病机制在很大程度上尚不清楚。代谢组学分析可以提供有关疾病病理生理学、候选生物标志物和潜在干预策略的全局信息。为了更好地了解 EP 的发病机制并探索 EP 的血清代谢特征,我们对 20 名 EP 患者和 20 名健康对照者进行了非靶向代谢组学分析。此外,我们还在 30 名 EP 患者和 30 名寻常型银屑病(PsV)患者的血清样本中进行了针对特定代谢物的靶向代谢组学分析。在非靶向分析中,从每个样本中提取了总共 2992 个分子特征,并获得了每个特征的峰强度。主成分分析(PCA),正交偏最小二乘判别分析(OPLS-DA)显示组间存在显著差异。筛选后,发现 EP 中有 98 种代谢物显著失调,其中下调 67 种,上调 31 种。EP 患者的 L-色氨酸、L-异亮氨酸、视黄醇、溶血磷脂酰胆碱(LPC)水平较低,甜菜碱和尿酸水平较高。KEGG 分析显示差异代谢物富集在氨基酸代谢和甘油磷脂代谢中。靶向代谢组学显示 EP 中的 L-色氨酸低于 PsV,差异具有统计学意义,且 L-色氨酸水平与 PASI 评分呈负相关。发现了 EP 的血清代谢特征。EP 中氨基酸和甘油磷脂代谢失调。代谢物差异为 EP 的发病机制提供了线索,它们可能为治疗干预提供了思路。