Metabolomics and lupus

OBJECTIVES: A timely diagnosis is imperative for curing cancer. However, in patients with rheumatic musculoskeletal diseases (RMDs) or paraneoplastic syndromes, misleading symptoms frequently delay cancer diagnosis. As metabolic remodelling characterises both cancer and RMD, we analysed if a metabolic signature can indicate paraneoplasia (PN) or reveal concomitant cancer in patients with RMD. METHODS: Metabolic alterations in the sera of rheumatoid arthritis (RA) patients with (n=56) or without (n=52) a history of invasive cancer were quantified by nuclear magnetic resonance analysis...

In classic semiquantitative metabolomics, metabolite intensities are affected by biological factors and other unwanted variations. A systematic evaluation of the data processing methods is crucial to identify adequate processing procedures for a given experimental setup. Current comparative studies are mostly focused on peak area data but not on absolute concentrations. In this study, we evaluated data processing methods to produce outputs that were most similar to the corresponding absolute quantified data...

BACKGROUND: Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. METHODS: Female MRL/ lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples...

INTRODUCTION: Pregnancy outcomes of patients with systemic lupus erythematosus (SLE) have improved over the past four decades, leading to an increased desire for pregnancy among this cohort. However, the offspring of patients with SLE still face the risks of preterm birth, low birth weight, learning disabilities, and neurological disorders, while the causes underlying these risks remain unclear. METHODS: In this study, we analyzed the blood metabolic features of neonates born to 30 SLE patients and 52 healthy control mothers by employing tandem mass spectrometry with the dual aims of identifying the etiology of metabolic features specific to infants born from mothers with SLE and providing new insights into the clinical management of such infants...

China, being a densely populated nation, faces a substantial economic burden due to a high incidence of lupus nephritis (LN) cases. The concealed onset of LN has resulted in many individuals have missed the optimal timing for treatment. The aim of the research is to study the serum metabolomics of Chinese LN patients using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS to identify potential diagnostic markers. Fifty LN patients and fifty normal controls, matched for Body Mass Index (BMI) and age, were selected...

OBJECTIVES: Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs). METHODS: Serum NMR metabolomic profiles from female SLE patients (n = 164, age = 14-76) and HCs (n = 123, age = 13-72) were assessed across age by linear regression and by age group between patients/HCs (Group-1, age ≤ 25, n = 62/46; Group-2, age = 26-49, n = 50/46; Group-3, age ≥ 50, n = 52/31) using multiple t-tests...

OBJECTIVE: Investigate the hypothesis that interferon (IFN) stimulated gene (ISG) expression in systemic lupus erythematosus (SLE) monocytes is linked to changes in metabolic reprogramming and epigenetic regulation of ISG expression. METHODS: Monocytes from healthy volunteers and SLE patients at baseline or following IFNα treatment were analyzed by extracellular flux analysis, proteomics, metabolomics, chromatin immunoprecipitation and gene expression. The histone demethylases KDM6A/B were inhibited using GSK-J4...

OBJECTIVES: Patients with juvenile-onset systemic lupus erythematosus (JSLE) have increased atherosclerosis risk. This study investigated novel atherosclerosis progression biomarkers in the APPLE trial, the largest investigator-led randomised control trial of atorvastatin versus placebo for atherosclerosis progression in JSLE, using carotid intima-media thickness (CIMT) as primary outcome. METHODS: Unsupervised clustering of baseline CIMT and CIMT-progression over 36 months was used to stratify JSLE patients...

Autoimmune diseases, characterized by the immune system's loss of self-tolerance, lack definitive diagnostic tests, necessitating the search for reliable biomarkers. This systematic review aims to identify common metabolite changes across multiple autoimmune diseases. Following PRISMA guidelines, we conducted a systematic literature review by searching MEDLINE, ScienceDirect, Google Scholar, PubMed, and Scopus (Elsevier) using keywords "Metabolomics", "Autoimmune diseases", and "Metabolic changes". Articles published in English up to March 2023 were included without a specific start date filter...

BACKGROUND: Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD. METHODS: A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD)...

PURPOSE: Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis. PATIENTS AND METHODS: The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which leads to the formation of immune complex deposits in multiple organs and has heterogeneous clinical manifestations. Currently, exosomes for liquid biopsy have been applied in diagnosis and monitoring of diseases, whereas SLE discrimination based on exosomes at the metabolic level is rarely reported. Herein, we constructed a protocol for metabolomic study of urinary exosomes from SLE patients and healthy controls (HCs) with high efficiency and throughput...

Activated lymphocyte-derived DNA (ALD-DNA) has been reported to drive the polarization of macrophages toward M2b, producing inflammatory cytokines and inducing inflammation, correspondingly playing an essential role in the development of systemic lupus erythematosus (SLE). Recently, accumulating evidence has pinpointed metabolic adaptation as the crucial cell-intrinsic determinant for inflammatory response, in which glucose metabolism is the key event. However, whether and how glucose metabolism was involved in ALD-DNA-induced macrophage inflammatory response and SLE development remains unclear...

There is a wide variety of autoimmune diseases (ADs) with complex pathogenesis and their accurate diagnosis is difficult to achieve because of their vague symptoms. Metabolomics has been proven to be an efficient tool in the analysis of metabolic disorders to provide clues about the mechanism and diagnosis of diseases. Previous studies of the metabolomics analysis of ADs were not competent in their discrimination. Herein, a liquid chromatography tandem mass spectrometry (LC-MS) strategy combined with machine learning is proposed for the discrimination and classification of ADs...

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, and several studies have suggested possible early RV involvement. Aim of the study was to evaluate the 3D echo parameters of the right ventricle (RV) and the metabolomic profile to correlate both with SLE severity. Forty SLE patients, free of cardiovascular disease, were enrolled and the following 3D parameters were evaluated: the RV ejection fraction (RV-EF), longitudinal strain of the interventricular septum (Septal LS), longitudinal strain of the free wall (Free-LS) and the fractional area change (FAC)...

Atherosclerosis and its main consequence, cardiovascular disease (CVD) are nowadays regarded as chronic inflammatory disease conditions, and CVD is the main cause of death in the world. Other examples of chronic inflammation are rheumatic and other autoimmune conditions, but also diabetes, obesity, and even osteoarthritis among others. In addition, infectious diseases can have traits in common with these conditions. Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, where atherosclerosis is increased and the risk of CVD is very high...

The expansion of follicular helper T (Tfh) cells, which is tightly associated with the development of lupus, is reversed by the inhibition of either glycolysis or glutaminolysis in mice. Here we analyzed the gene expression and metabolome of Tfh cells and naive CD4+ T (Tn) cells in the B6. Sle1.Sle2.Sle3 (triple congenic, TC) mouse model of lupus and its congenic B6 control. Lupus genetic susceptibility in TC mice drives a gene expression signature starting in Tn cells and expanding in Tfh cells with enhanced signaling and effector programs...

Systemic lupus erythematosus (SLE) is caused by a combination of genetic and environmental factors. Recently, analysis of a functional genome database of genetic polymorphisms and transcriptomic data from various immune cell subsets revealed the importance of the oxidative phosphorylation (OXPHOS) pathway in the pathogenesis of SLE. In particular, activation of the OXPHOS pathway is persistent in inactive SLE, and this activation is associated with organ damage. The finding that hydroxychloroquine (HCQ), which improves the prognosis of SLE, targets toll-like receptor (TLR) signaling upstream of OXPHOS suggests the clinical importance of this pathway...

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterized by multiple organ damage accompanied by the over-production of autoantibodies. Decreased intestinal flora diversity and disruption of homeostasis have been proven to be associated with pathogenesis of SLE. In previous study, a clinical trial was conducted to verify the safety and effectiveness of fecal microbiota transplantation (FMT) in the treatment of SLE. To explore the mechanism of FMT in the treatment of SLE, we included 14 SLE patients participating in clinical trials, including 8 in responders group (Rs) and 6 in non-responders group (NRs), and collected peripheral blood DNA and serum...

The aims of this study were in systemic lupus erythematosus (SLE) patients: 1) to compare the metabolomic profile of insulin resistance (IR) with controls and 2) to correlate the metabolomic profile with other IR surrogates and SLE disease variables and vitamin levels. In this cross-sectional study, serum samples were collected from women with SLE (n= 64) and gender- and age-matched controls (n= 71), which were not diabetic. Serum metabolomic profiling was performed using UPLC-MS-MS (Quantse score). HOMA and QUICKI were carried out...