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代谢组学特征及血清多不饱和脂肪酸代谢在白癜风患者中的潜在应用。

Metabolomics Signature and Potential Application of Serum Polyunsaturated Fatty Acids Metabolism in Patients With Vitiligo.

机构信息

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Department of Dermatology, The Medical Center of Air Force of People's Liberation Army, Forth Military Medical University, Beijing, China.

出版信息

Front Immunol. 2022 Feb 10;13:839167. doi: 10.3389/fimmu.2022.839167. eCollection 2022.

Abstract

Vitiligo is a depigmented skin disorder caused by a variety of factors, including autoimmune, metabolic disturbance or their combined effect, etc. Non-targeted metabolomic analyses have denoted that dysregulated fatty acids metabolic pathways are involved in the pathogenesis of vitiligo. However, the exact category of fatty acids that participate in vitiligo development and how they functionally affect CD8 T cells remain undefined. We aimed to determine the difference in specific fatty acids among vitiligo patients and healthy individuals and to investigate their association with clinical features in patients with vitiligo. Serum levels of fatty acids in 48 vitiligo patients and 28 healthy individuals were quantified by performing ultra-performance liquid chromatography-tandem mass spectrometry. Univariate and multivariate analyses were carried out to evaluate the significance of differences. Moreover, flow cytometry was used to explore the effect of indicated fatty acids on the function of CD8 T cells derived from patients with vitiligo. We demonstrated that serological level of alpha-linolenic acid (ALA) was markedly upregulated, while that of arachidonic acid (ARA), arachidic acid (AA) and behenic acid were significantly downregulated in patients with vitiligo. Moreover, ALA levels were positively associated with vitiligo area scoring index (VASI) and ARA was a probable biomarker for vitiligo. We also revealed that supplementation with ARA or nordihydroguaiaretic acid (NDGA) could suppress the function of CD8 T cells. Our results showed that vitiligo serum has disorder-specific phenotype profiles of fatty acids described by dysregulated metabolism of polyunsaturated fatty acids. Supplementation with ARA or NDGA might promote vitiligo treatment. These findings provide novel insights into vitiligo pathogenesis that might add to therapeutic options.

摘要

白癜风是一种由多种因素引起的色素减退性皮肤疾病,包括自身免疫、代谢紊乱或它们的联合作用等。非靶向代谢组学分析表明,失调的脂肪酸代谢途径参与了白癜风的发病机制。然而,确切参与白癜风发展的脂肪酸类别以及它们如何对 CD8 T 细胞产生功能影响仍不清楚。我们旨在确定白癜风患者和健康个体之间特定脂肪酸的差异,并研究它们与白癜风患者临床特征的关联。通过超高效液相色谱-串联质谱法对 48 名白癜风患者和 28 名健康个体的血清脂肪酸水平进行定量分析。进行单变量和多变量分析以评估差异的显著性。此外,使用流式细胞术探索指示脂肪酸对来自白癜风患者的 CD8 T 细胞功能的影响。我们证明了血清中α-亚麻酸 (ALA) 的水平显著上调,而花生四烯酸 (ARA)、花生酸 (AA) 和山嵛酸 (BA) 的水平则显著下调。此外,ALA 水平与白癜风面积评分指数 (VASI) 呈正相关,ARA 可能是白癜风的一个潜在生物标志物。我们还发现,补充 ARA 或去甲二氢愈创木酸 (NDGA) 可以抑制 CD8 T 细胞的功能。我们的研究结果表明,白癜风血清具有由多不饱和脂肪酸代谢失调描述的特定疾病表型的脂肪酸特征谱。补充 ARA 或 NDGA 可能促进白癜风的治疗。这些发现为白癜风发病机制提供了新的见解,可能为治疗选择增添新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee26/8866849/29eec22c41f5/fimmu-13-839167-g001.jpg

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