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metabolomic and 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 (GC/MS) in conjunction with multivariate statistical analysis, and possible biomarker metabolites were identified...
February 26, 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
Rossana Scrivo, Luca Casadei, Mariacristina Valerio, Roberta Priori, Guido Valesini, Cesare Manetti
Metabolomics is the analysis of the concentration profiles of low molecular weight compounds present in biological fluids. Metabolites are nonpeptide molecules representing the end products of cellular activity. Therefore, changes in metabolite concentrations reveal the range of biochemical effects induced by a disease or its therapeutic intervention. Metabolomics has recently become feasible with the accessibility of new technologies, including mass spectrometry and high-resolution proton nuclear magnetic resonance, and has already been applied to several disorders...
June 2014: Current Allergy and Asthma Reports
Xinghong Ding, Jinbo Hu, Chengping Wen, Zhishan Ding, Li Yao, Yongsheng Fan
Jieduquyuziyin prescription (JP), a traditional Chinese medicine (TCM) prescription, has been widely used for the clinical treatment of systemic lupus erythematosus (SLE). However, the complex chemical constituents of JP and the multifactorial pathogenesis of SLE make research on the therapeutic mechanism of JP in SLE challenging. In this paper, a serum metabolomics approach based on rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF/MS) was employed to acquire the metabolic characteristics of serum samples obtained from mice in the SLE model group, JP-treated group, prednisone acetate (PA)-treated group and control group...
2014: PloS One
Roberta Priori, Rossana Scrivo, Jessica Brandt, Mariacristina Valerio, Luca Casadei, Guido Valesini, Cesare Manetti
Metabolomics belongs to the family of "-omics" sciences, also comprised of genomics, transcriptomics, and proteomics, all of which share the advantage of a non-targeted approach for identifying biomarkers and profiling the patient. This means that they do not require a preliminary knowledge of the substances to be studied. Moreover, even small quantities of biological fluids or tissues may be utilized for analysis. Metabolomic procedure has become feasible only recently with the advent and accessibility of new high-throughput technologies, including mass spectrometry and nuclear magnetic resonance...
August 2013: Autoimmunity Reviews
W Sui, X Hou, W Che, M Yang, Y Dai
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies directed against nuclear self-antigens and circulating immune complexes. This results in damages to various organs or systems, including skin, joints, kidneys and the central nervous system. Clinical manifestations of SLE could be diverse, including glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures and arthritis. The complicated pathogenesis and varied clinical symptoms of SLE pose great challenges in the diagnosis and monitoring of this disease...
April 2013: Genes and Immunity
Tianfu Wu, Chun Xie, Jie Han, Yujin Ye, Jim Weiel, Quan Li, Irene Blanco, Chul Ahn, Nancy Olsen, Chaim Putterman, Ramesh Saxena, Chandra Mohan
The metabolic disturbances that underlie systemic lupus erythematosus are currently unknown. A metabolomic study was executed, comparing the sera of 20 SLE patients against that of healthy controls, using LC/MS and GC/MS platforms. Validation of key differences was performed using an independent cohort of 38 SLE patients and orthogonal assays. SLE sera showed evidence of profoundly dampened glycolysis, Krebs cycle, fatty acid β oxidation and amino acid metabolism, alluding to reduced energy biogenesis from all sources...
2012: PloS One
Fei Li, Andrew D Patterson, Kristopher W Krausz, Bernhard Dick, Felix J Frey, Frank J Gonzalez, Jeffrey R Idle
Procainamide, a type I antiarrhythmic agent, is used to treat a variety of atrial and ventricular dysrhythmias. It was reported that long-term therapy with procainamide may cause lupus erythematosus in 25-30% of patients. Interestingly, procainamide does not induce lupus erythematosus in mouse models. To explore the differences in this side-effect of procainamide between humans and mouse models, metabolomic analysis using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) was conducted on urine samples from procainamide-treated humans, CYP2D6-humanized mice, and wild-type mice...
May 15, 2012: Biochemical Pharmacology
Lindsey E Romick-Rosendale, Hermine I Brunner, Michael R Bennett, Rina Mina, Shannen Nelson, Michelle Petri, Adnan Kiani, Prasad Devarajan, Michael A Kennedy
INTRODUCTION: Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making...
2011: Arthritis Research & Therapy
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