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Metabolomics and lupus

Cameron B Speyer, Karen H Costenbader
Systemic lupus erythematosus (SLE) is a multi-system inflammatory autoimmune disease of incompletely understood etiology. It is thought that environmental exposures "trigger" or accelerate the disease in genetically-predisposed individuals. Areas covered: Substantial epidemiological evidence exists to support the association between cigarette smoking and the risk of incident SLE. Recent evidence points to current smoking as the specific risk factor, with decreasing risk 5 years after smoking cessation, and the greatest risk for disease characterized by the presence of SLE- specific autoantibodies...
May 3, 2018: Expert Review of Clinical Immunology
Yan Liang, Shang-Bo Xie, Chang-Hao Wu, Yuan Hu, Qin Zhang, Si Li, Yin-Guang Fan, Rui-Xue Leng, Hai-Feng Pan, Hua-Bao Xiong, Dong-Qing Ye
This study was conducted to (1) characterize coagulation cascade and complement system in systemic lupus erythematosus (SLE); (2) evaluate the associations between coagulation cascade, complement system, inflammatory response and SLE disease severity; (3) test the diagnostic value of a combination of D-dimer and C4 for lupus activity. Transcriptomics, proteomics and metabolomics were performed in 24 SLE patients and 24 healthy controls. The levels of ten coagulations, seven complements and three cytokines were measured in 112 SLE patients...
March 13, 2018: Oncotarget
Juan-Manuel Anaya, Paula Restrepo-Jiménez, Carolina Ramírez-Santana
PURPOSE OF REVIEW: The autoimmune ecology refers to the interactions between individuals and their environment leading to a breakdown in immune tolerance and, therefore, to the development of one or more autoimmune diseases in such an individual. Herein, an update is offered on four specific factors associated with autoimmune diseases, namely, vitamin D, smoking, alcohol and coffee consumption from the perspective of exposome and metabolomics. RECENT FINDINGS: Smoking is associated with an increased risk for most of the autoimmune diseases...
February 12, 2018: Current Opinion in Rheumatology
Izabella Surowiec, Erik Johansson, Frida Torell, Helena Idborg, Iva Gunnarsson, Elisabet Svenungsson, Per-Johan Jakobsson, Johan Trygg
INTRODUCTION: Availability of large cohorts of samples with related metadata provides scientists with extensive material for studies. At the same time, recent development of modern high-throughput 'omics' technologies, including metabolomics, has resulted in the potential for analysis of large sample sizes. Representative subset selection becomes critical for selection of samples from bigger cohorts and their division into analytical batches. This especially holds true when relative quantification of compound levels is used...
2017: Metabolomics: Official Journal of the Metabolomic Society
Jing Wei, Jun Gao, Xinghong Ding
A urine metabolomics method based on gas chromatography-mass spectrometry was developed in order to investigate the metabolite characteristics of systemic lupus erythematosus (SLE) and the therapeutic effects of Jieduquyuziyin prescription. The urinary metabolic profiles in urine specimens of the SLE model mice (MRL/lpr) group, prednisone acetate-treated SLE mouse group, Jieduquyuziyin prescription-treated SLE mouse group, and control group (C57BL/6 J) after the administration were analyzed by gas chromatography-mass spectrometry...
February 2018: Biomedical Chromatography: BMC
Juntuo Zhou, Chunlei Liu, Dandan Si, Bing Jia, Lijun Zhong, Yuxin Yin
Advances in high-resolution mass spectrometers with faster scanning capabilities and higher sensitivities have expanded these instruments' functionality beyond traditional data-dependent acquisition in targeted metabolomics. Apart from the traditional multiple reaction monitoring strategy, the parallel reaction monitoring (PRM) strategy is also used for targeted metabolomics quantification. The high resolution and mass accuracy of full-scan (MS1) and tandem mass spectrometry (MS/MS) scan result in sufficient selectivity by monitoring all MS/MS fragment ions for each target precursor and simultaneously providing flexibility in assay method construction and post-acquisition data analysis...
June 15, 2017: Analytica Chimica Acta
J Li, X-W Xie, H Zhou, B Wang, M-J Zhang, F-Y Tang
Metabolomics has been applied to explore altered metabolite profiles in disease and identify unique metabolic signatures specific to certain pathologies. The aim of the current study is to characterize the metabolic profile of patients diagnosed with lupus nephritis (LN) and explore new insights into underlying disease processes. A metabolomic approach using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS) was developed in serum samples from 32 LN patients, 30 idiopathic nephrotic syndrome (INS) patients and 28 healthy controls (HCs)...
October 2017: Lupus
Anupam Guleria, Avadhesh Pratap, Durgesh Dubey, Atul Rawat, Smriti Chaurasia, Edavalath Sukesh, Sanat Phatak, Sajal Ajmani, Umesh Kumar, Chunni Lal Khetrapal, Paul Bacon, Ramnath Misra, Dinesh Kumar
Management of patient with Lupus Nephritis (LN) continues to remain a challenge for the treating physicians because of considerable morbidity and even mortality. The search of biomarkers in serum and urine is a focus of researchers to unravel new targets for therapy. In the present study, the utility of NMR-based serum metabolomics has been evaluated for the first time in discriminating LN patients from non-nephritis lupus patients (SLE) and further to get new insights into the underlying disease processes for better clinical management...
October 14, 2016: Scientific Reports
Arnald Alonso, Antonio Julià, Maria Vinaixa, Eugeni Domènech, Antonio Fernández-Nebro, Juan D Cañete, Carlos Ferrándiz, Jesús Tornero, Javier P Gisbert, Pilar Nos, Ana Gutiérrez Casbas, Lluís Puig, Isidoro González-Álvaro, José A Pinto-Tasende, Ricardo Blanco, Miguel A Rodríguez, Antoni Beltran, Xavier Correig, Sara Marsal
BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn's disease, and ulcerative colitis...
September 8, 2016: BMC Medicine
Anders A Bengtsson, Johan Trygg, Dirk M Wuttge, Gunnar Sturfelt, Elke Theander, Magdalena Donten, Thomas Moritz, Carl-Johan Sennbro, Frida Torell, Christian Lood, Izabella Surowiec, Stefan Rännar, Torbjörn Lundstedt
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diagnose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases...
2016: PloS One
Bei Yan, Jia Huang, Fan Dong, Liping Yang, Cibo Huang, Ming Gao, Aixin Shi, Weibin Zha, Luyi Shi, Xin Hu
Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous organ and system manifestations. In this study, urinary metabolic alterations related to SLE were investigated by performing gas chromatography/mass spectrometry (GC/MS) based metabolomics and multivariate statistical analysis. Patients with SLE and healthy controls could be clearly differentiated in view of the metabolic abnormity in urine. Among 70 identified endogenous metabolites, 23 metabolites were dramatically increased in SLE patients, which involved in several key metabolic pathways including energy metabolism, nucleotide metabolism, oxidative stress and gut-microbiome-derived metabolism...
November 2016: Biomedical Chromatography: BMC
Bei Yan, Jia Huang, Chunmei Zhang, Xin Hu, Ming Gao, Aixin Shi, Weibin Zha, Luyi Shi, Cibo Huang, Liping Yang
OBJECTIVES: The aim of this study is to characterize the serum metabolic profiles of patients with systemic lupus erythematosus (SLE) using metabolomics. METHODS: Serum samples were collected from patients with SLE (n = 80) and gender- and age-matched healthy controls (n = 57). Metabolite profiles were performed with gas chromatography-mass spectrometry in conjunction with multivariate statistical analysis, and possible biomarker metabolites were identified...
November 2016: Modern Rheumatology
Jun Saegusa, Seiji Kawano, Akio Morinobu
Metabolomics is the identification and quantification of the metabolome, all low-molecular-weight metabolites in a biological sample. Cell metabolism is known to have a marked impact on the function of various immune cells. We recently examined the differences in the serum metabolome between patients with systemic lupus erythematosus (SLE) and healthy subjects, using gas chromatography/mass spectrometry (GC/MS), and sought to identify candidates for metabolic biomarkers. We found that the levels of 25 metabolites were significantly different in SLE patients compared to healthy controls...
April 2015: Rinsho Byori. the Japanese Journal of Clinical Pathology
Andras Perl, Robert Hanczko, Zhi-Wei Lai, Zachary Oaks, Ryan Kelly, Rebecca Borsuk, John M Asara, Paul E Phillips
Systemic lupus erythematosus (SLE) patients exhibit depletion of the intracellular antioxidant glutathione and downstream activation of the metabolic sensor, mechanistic target of rapamycin (mTOR). Since reversal of glutathione depletion by the amino acid precursor, N-acetylcysteine (NAC), is therapeutic in SLE, its mechanism of impact on the metabolome was examined within the context of a double-blind placebo-controlled trial. Quantitative metabolome profiling of peripheral blood lymphocytes (PBL) was performed in 36 SLE patients and 42 healthy controls matched for age, gender, and ethnicity of patients using mass spectrometry that covers all major metabolic pathways...
2015: Metabolomics: Official Journal of the Metabolomic Society
Cristina Arriens, Linda S Hynan, Robert H Lerman, David R Karp, Chandra Mohan
INTRODUCTION: A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus (SLE) found reduction of antioxidants and substrates for energy generation. These metabolic alterations may underlie one of the most common features of SLE--fatigue. The metabolomic studies also noted reduced omega-3 fatty acids, which are powerful anti- oxidants. This deficiency may be causally related to oxidative stress, inflammation, disease activity, and fatigue in SLE. Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies...
August 18, 2015: Nutrition Journal
Jill P Buyon, Phillip Cohen, Joan T Merrill, Gary Gilkeson, Mariana Kaplan, Judith James, W Joseph McCune, Sasha Bernatsky, Keith Elkon
This review describes eight 'great ideas' regarding bench-to-bedside considerations in systemic lupus erythematosus (SLE) presented at the second international LUPUS meeting in Quebec, September 2014. The topics included: correcting the impaired clearance of apoptotic fragments; optimisation of clinical trial design: the PERFECT (Pre Evaluation Reducing Frighteningly Elevated Coverable Targets) study; lipidomics and metabolomics in SLE; importance of the inflammasome; identification and treatment of asymptomatic autoimmunity: prevention of SLE; combining low doses of hydroxychloroquine and quinacrine for long-term maintenance therapy of SLE; reducing emergency room visits and the critical relevance of the autoantigen...
2015: Lupus Science & Medicine
Zhen Yang, Eric L Matteson, Jörg J Goronzy, Cornelia M Weyand
Cancer cells have long been known to fuel their pathogenic growth habits by sustaining a high glycolytic flux, first described almost 90 years ago as the so-called Warburg effect. Immune cells utilize a similar strategy to generate the energy carriers and metabolic intermediates they need to produce biomass and inflammatory mediators. Resting lymphocytes generate energy through oxidative phosphorylation and breakdown of fatty acids, and upon activation rapidly switch to aerobic glycolysis and low tricarboxylic acid flux...
2015: Arthritis Research & Therapy
David Rojo, Arancha Hevia, Rafael Bargiela, Patricia López, Adriana Cuervo, Sonia González, Ana Suárez, Borja Sánchez, Mónica Martínez-Martínez, Christian Milani, Marco Ventura, Coral Barbas, Andrés Moya, Antonio Suárez, Abelardo Margolles, Manuel Ferrer
Multiple factors have been shown to alter intestinal microbial diversity. It remains to be seen, however, how multiple collective pressures impact the activity in the gut environment and which, if any, is positioned as a dominant driving factor determining the final metabolic outcomes. Here, we describe the results of a metabolome-wide scan of gut microbiota in 18 subjects with systemic lupus erythematosus (SLE) and 17 healthy control subjects and demonstrate a statistically significant difference (p < 0...
2015: Scientific Reports
Jeffrey A Sparks, Karen H Costenbader
Rheumatic diseases offer distinct challenges to researchers because of heterogeneity in disease phenotypes, low disease incidence, and geographic variation in genetic and environmental factors. Emerging research areas, including epigenetics, metabolomics, and the microbiome, may provide additional links between genetic and environmental risk factors in the pathogenesis of rheumatic disease. This article reviews the methods used to establish genetic and environmental risk factors and studies gene-environment interactions in rheumatic diseases, and provides specific examples of successes and challenges in identifying gene-environment interactions in rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis...
November 2014: Rheumatic Diseases Clinics of North America
Cristina Arriens, Chandra Mohan
Systemic lupus erythematosus is a complex autoimmune disease affecting multiple organ systems. Currently, diagnosis relies upon meeting at least four out of eleven criteria outlined by the ACR. The scientific community actively pursues discovery of novel diagnostics in the hope of better identifying susceptible individuals in early stages of disease. Comprehensive studies have been conducted at multiple biological levels including: DNA (or genomics), mRNA (or transcriptomics), protein (or proteomics) and metabolites (or metabolomics)...
December 1, 2013: International Journal of Clinical Rheumatology
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