皮肤型红斑狼疮的代谢谱在烟酰胺腺嘌呤二核苷酸途径中存在异常。

Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.

作者信息

Abbas Laila F, Barber Grant, Lu Grace, Chamseddin Bahir, Vu Hieu, Cai Ling, Srivastava Divya, Nijhawan Rajiv L, Wang Richard C, Chong Benjamin F

机构信息

Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Children's Medical Center Research Institute, University of Texas Southwestern, Dallas, Texas, USA.

出版信息

Lupus Sci Med. 2025 Jan 25;12(1):e001401. doi: 10.1136/lupus-2024-001401.

DOI:10.1136/lupus-2024-001401

PMID:39863305

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11784198/

Abstract

OBJECTIVE

Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).

METHODS

This was a cross-sectional pilot study comparing metabolomic sera and skin profiles of patients with CLE and normal controls. Patients were recruited from outpatient dermatology clinics at the University of Texas Southwestern and Parkland Health in Dallas, Texas, from January 2019 to October 2020. Skin and serum samples underwent LC-MS analysis. Disease sample metabolite levels were compared with controls, with significance levels adjusted for multiple hypothesis testing.

RESULTS

17 serum samples (9 CLE, 8 control) and 11 skin samples (5 CLE, 6 control) were analysed using LC-MS, yielding 313 known unique metabolic structures from CLE samples. Patients with CLE were found to have 11 metabolites of differential abundance in the skin, but only 2 in the sera. CLE skin showed increased levels of citrulline (log fold change (FC)=1.15, p=0.02) and uracil (logFC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (logFC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (logFC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD) (logFC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (logFC=1.17, p=0.02) and cystine (logFC=1.04, p=0.03) compared with control sera.

CONCLUSIONS

Metabolites associated with the NAD pathway may be dysregulated in the skin of patients with CLE. Available treatments including nicotinamide supplementation and anti-CD38 biologics that can correct these abnormalities can be further investigated in patients with CLE.

摘要

目的

代谢重编程在调节先天性和适应性免疫反应中起关键作用，但其在皮肤自身免疫性疾病（如皮肤红斑狼疮（CLE））中的作用研究较少。更好地了解CLE中失调的代谢途径可能会带来新的治疗选择、生物标志物，并深入了解疾病发病机制。目的是使用液相色谱 - 质谱联用（LC - MS）比较CLE患者和对照患者皮肤及血清中的代谢组学特征。

方法

这是一项横断面试点研究，比较CLE患者和正常对照的代谢组学血清及皮肤特征。2019年1月至2020年10月期间，从德克萨斯大学西南医学中心和德克萨斯州达拉斯帕克兰健康中心的门诊皮肤科诊所招募患者。对皮肤和血清样本进行LC - MS分析。将疾病样本代谢物水平与对照进行比较，并对多重假设检验的显著性水平进行调整。

结果

使用LC - MS分析了17份血清样本（9份CLE，8份对照）和11份皮肤样本（5份CLE，6份对照），从CLE样本中得到313种已知的独特代谢结构。发现CLE患者皮肤中有11种代谢物丰度存在差异，而血清中只有2种。与对照皮肤相比，CLE皮肤中瓜氨酸水平升高（对数倍变化（FC）=1.15，p = 0.02）和尿嘧啶水平升高（对数倍变化=1.79，p = 0.04），而环磷酸腺苷核糖（cADPr）（对数倍变化=0.83，p = 0.04）、烟酰胺单核苷酸（NMN）（对数倍变化=0.75，p = 0.016）和烟酰胺腺嘌呤二核苷酸（NAD）（对数倍变化=0.86，p = 0.016）下调。与对照血清相比，CLE血清中阿拉伯糖（对数倍变化=1.17，p = 0.02）和胱氨酸（对数倍变化=1.04，p = 0.03）增加。