Laila F Abbas, Grant Barber, Grace Lu, Bahir Chamseddin, Hieu Vu, Ling Cai, Divya Srivastava, Rajiv L Nijhawan, Richard C Wang, Benjamin F Chong
{"title":"皮肤狼疮的代谢谱在烟酰胺腺嘌呤二核苷酸途径中有异常。","authors":"Laila F Abbas, Grant Barber, Grace Lu, Bahir Chamseddin, Hieu Vu, Ling Cai, Divya Srivastava, Rajiv L Nijhawan, Richard C Wang, Benjamin F Chong","doi":"10.1136/lupus-2024-001401","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>2</sub> fold change (FC)=1.15, p=0.02) and uracil (log<sub>2</sub>FC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (log<sub>2</sub>FC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (log<sub>2</sub>FC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD<sup>+</sup>) (log<sub>2</sub>FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log<sub>2</sub>FC=1.17, p=0.02) and cystine (log<sub>2</sub>FC=1.04, p=0.03) compared with control sera.</p><p><strong>Conclusions: </strong>Metabolites associated with the NAD<sup>+</sup> 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.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784198/pdf/","citationCount":"0","resultStr":"{\"title\":\"Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.\",\"authors\":\"Laila F Abbas, Grant Barber, Grace Lu, Bahir Chamseddin, Hieu Vu, Ling Cai, Divya Srivastava, Rajiv L Nijhawan, Richard C Wang, Benjamin F Chong\",\"doi\":\"10.1136/lupus-2024-001401\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>2</sub> fold change (FC)=1.15, p=0.02) and uracil (log<sub>2</sub>FC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (log<sub>2</sub>FC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (log<sub>2</sub>FC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD<sup>+</sup>) (log<sub>2</sub>FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log<sub>2</sub>FC=1.17, p=0.02) and cystine (log<sub>2</sub>FC=1.04, p=0.03) compared with control sera.</p><p><strong>Conclusions: </strong>Metabolites associated with the NAD<sup>+</sup> 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.</p>\",\"PeriodicalId\":18126,\"journal\":{\"name\":\"Lupus Science & Medicine\",\"volume\":\"12 1\",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-01-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784198/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lupus Science & Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/lupus-2024-001401\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lupus Science & Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/lupus-2024-001401","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.
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 (log2 fold change (FC)=1.15, p=0.02) and uracil (log2FC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (log2FC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (log2FC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD+) (log2FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log2FC=1.17, p=0.02) and cystine (log2FC=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.
期刊介绍：
Lupus Science & Medicine is a global, peer reviewed, open access online journal that provides a central point for publication of basic, clinical, translational, and epidemiological studies of all aspects of lupus and related diseases. It is the first lupus-specific open access journal in the world and was developed in response to the need for a barrier-free forum for publication of groundbreaking studies in lupus. The journal publishes research on lupus from fields including, but not limited to: rheumatology, dermatology, nephrology, immunology, pediatrics, cardiology, hepatology, pulmonology, obstetrics and gynecology, and psychiatry.
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