A5027586408- Systemic Lupus Erythematosus Research
- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Immune Response and Inflammation
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- Cardiovascular Health and Risk Factors
- Renal Diseases and Glomerulopathies
- Systemic Sclerosis and Related Diseases
- Lipid metabolism and disorders
- Computational Drug Discovery Methods
- Complement system in diseases
- Cytokine Signaling Pathways and Interactions
- Advanced Statistical Process Monitoring
- interferon and immune responses
- Immunotherapy and Immune Responses
- Peroxisome Proliferator-Activated Receptors
- Quality and Management Systems
- Digestive system and related health
- Multiple Sclerosis Research Studies
- Pregnancy and Medication Impact
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2016-2024
National Institutes of Health
2017-2024
Government of the United States of America
2022
National Heart Lung and Blood Institute
2018
Office of the Director
2016
Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chiT-bet+ subset, with a unique expression profile including chemokine receptors consistent migration to target tissues, expanded in SLE patients, present nephrotic kidney, enriched for autoreactive specificities and correlates defined clinical manifestations. IL-21 can potently induce cells promote differentiation these into...
Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE characterized by elevated levels a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, heterogeneity LDGs remain to be systematically determined. Transcriptomics epigenetic assessment LDGs, autologous normal-density neutrophils, healthy control neutrophils was performed bulk single-cell RNA sequencing assay for transposase-accessible...
Abstract Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled trial SLE subjects (ClinicalTrials.gov NCT02535689). study, 30 are randomized...
BACKGROUND. Systemic lupus erythematosus (SLE) is associated with enhanced risk of atherosclerotic cardiovascular disease not explained by Framingham score (FRS). Immune dysregulation to a distinct subset proinflammatory neutrophils (low density granulocytes; LDGs) may play key roles in conferring CV risk. This study assessed if LDGs are vivo vascular dysfunction and inflammation coronary plaque.
Objectives The presence of proinflammatory low-density granulocytes (LDG) has been demonstrated in autoimmune and infectious diseases. Recently, regulatory neutrophilic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) were identified systemic lupus erythematosus (SLE). Because LDG PMN-MDSC share a similar phenotype with contrasting functional effects, we explored these cohort patients SLE. Methods normal-density (NDG) isolated from fresh blood healthy donors (HD) Associations...
Anticytokine autoantibodies occur across a range of hematologic, pulmonary, and infectious diseases. However, systematic investigation their presence significance in autoimmune diseases is lacking. This study was undertaken to examine the distinct functions anticytokine patients with systemic lupus erythematosus (SLE) compared other rheumatic healthy controls.Serum samples from SLE (n = 199), primary Sjögren's syndrome (SS) 150), rheumatoid arthritis (RA) 149), controls 200) were screened...
To assess if ubiquitinated proteins potentially present in neutrophil extracellular traps (NETs) can modify cellular responses and induce inflammatory mechanisms patients with systemic lupus erythematosus (SLE) healthy subjects.We studied 74 subjects SLE 77 controls. Neutrophils low-density granulocytes were isolated, NETs induced. Ubiquitin content was quantified by western blot analysis, ELISA immunofluorescence microscopy, while ubiquitination of NET assessed immunoprecipitation....
Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking immune function intimately linked to cellular biophysical properties. This study used proteomic, biomechanical functional analyses further define neutrophil heterogeneity the context SLE.Proteomic/phosphoproteomic were performed healthy control (HC) normal density (NDNs), SLE NDNs autologous LDGs. The properties these...
Objective Autoreactive IgE antibodies have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesize that omalizumab, a monoclonal antibody binding IgE, may improve SLE activity by reducing type I interferon (IFN) production hampering plasmacytoid dendritic cells and basophil activation. This study was undertaken to assess safety, tolerability, clinical efficacy omalizumab mild moderate SLE. Methods Sixteen subjects with Systemic Lupus Erythematosus Disease...
Recent evidence indicates that high-density lipoprotein (HDL) exerts vasculoprotective activities by promoting activating transcription factor 3 (ATF3), leading to downregulation of toll-like receptor (TLR)-induced inflammatory responses. Systemic lupus erythematosus (SLE) is associated with increased cardiovascular disease risk not explained the Framingham score. studies have indicated oxidised HDL as a possible contributor. We investigated potential mechanisms which may lose its...
The Krebs cycle enzyme aconitate decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Previously, we reported that administration of 4-octyl to lupus-prone mice abrogated immune dysregulation clinical features. In this study, explore the role endogenous ACOD1/itaconate pathway development TLR7-induced lupus (imiquimod [IMQ] model). We found that, vitro, ACOD1 was induced mouse bone marrow-derived macrophages human monocyte-derived following TLR7 stimulation....
Background The associations between individual cardiovascular disease risk factors and leukocyte telomere length ( LTL ) have been inconclusive. We investigated the association overall health CVH as defined by American Heart Association whether is modified sex race/ethnicity. Methods Results included 5194 adults (aged ≥20) from National Health Nutrition Examination Survey 1999–2002. was a composite score of 7 metrics (smoking, physical activity, diet, body mass index, blood pressure, total...
Traditional cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia and diabetes do not explain the increased CVD burden in systemic lupus erythematosus (SLE). The oxidized-LDL receptor, LOX-1, is an inflammation-induced receptor implicated atherosclerotic plaque formation acute coronary syndrome, here we evaluated its role SLE-associated CVD. SLE patients have sLOX-1 levels which were associated with elevated proinflammatory HDL, oxLDL hsCRP. Interestingly, early...
Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described date. Immune dysregulation metabolic disturbances appear play prominent roles the induction of vascular disease SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses damage immune murine improves endothelial dysfunction other inflammatory diseases. We hypothesised that PGZ could improve...
Summary Systemic lupus erythematosus (SLE) is a complex autoimmune disorder whose pathology involves multiple immune cell types, including B and T lymphocytes as well myeloid cells. While it clear that autoantibody-producing cells, CD4+ help, are key contributors to disease, little known regarding the role of innate lymphoid cells such natural killer (NK) in pathogenesis SLE. We have characterized phenotype NK by multi-color flow cytometry large cohort SLE patients. overall percentage was...
Abstract Type I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Using a novel protocol generated 1,132 aptamer-based protein measurements anti-dsDNA pos SLE blood samples derived an signature (IFNPS) that approximates 21-gene (IFNGS). Of 82 patients with...
Subjects with SLE display an enhanced risk of atherosclerotic cardiovascular disease (CVD) that is not explained by Framingham risk. This study sought to investigate the utility nuclear MR (NMR) spectroscopy measurements serum lipoprotein particle counts and size glycoprotein acetylation (GlycA) burden predict coronary atherosclerosis in SLE. Coronary plaque was assessed subjects healthy controls using CT angiography. Lipoproteins GlycA were quantified NMR spectroscopy. displayed...
<h3>Background</h3> A pharmacologic intervention that modulates JAK/STAT signaling pathways represents a novel approach for the treatment of Systemic Lupus Erythematosus (SLE). In animal models SLE, tofacitinib improved clinical features, immune dysregulation and vascular dysfunction. The STAT4 risk allele is associated with higher severe manifestations in SLE. We hypothesized modulation response to inhibition would be more robust SLE subjects carry allele. <h3>Methods</h3> conducted phase...
An important pathogenic role for neutrophils in systemic lupus erythematosus (SLE) has been proposed. Neutrophils that lack brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (
Background:Infection is common cause of morbidity and mortality in SLE. Our objective was to determine incidence types infections, particularly opportunistic SLE patients receiving cyclophosphamide, identify contribution variables like demographics, steroid, other immunosuppressives, white blood cell absolute neutrophil count infection risk.Patients Methods: We did retrospective chart review our institute over last 10 years, who received minimum six cyclophosphamide infusions. Types...
The Krebs cycle enzyme Aconitate Decarboxylase 1 (ACOD1) mediates itaconate synthesis in myeloid cells.. Previously, we reported that administration of 4-octyl abrogated lupus phenotype mice. Here, explore the role endogenous ACOD1/itaconate pathway development murine as well their relevance premature cardiovascular damage SLE.
In patients with systemic lupus erythematosus (SLE), fatigue is a debilitating symptom poorly understood pathophysiology. Cardiorespiratory dysfunction has been hypothesised as contributor to SLE-fatigue. The purpose of this exploratory study was examine changes in cardiorespiratory function, following an exercise training programme women SLE, together patient reported outcomes and other pathophysiological measures that may underlie Sixteen SLE (Fatigue Severity Scale (FSS) ≥3) were enrolled...
Abstract We examined a large cohort of systemic lupus erythematosus (SLE) patients and found an unusual B cell subset highly expanded. These cells displayed unique phenotype expressed antigens not present on other populations, including high densities CD11c, FcRL5, the T-box transcription factor, T-bet, but unexpectedly, were CD40lo CD24−. Although these CD11chi largely negative for memory antigen CD27, their telomere length was consistent with memory, rather than naïve cells. Notably,...
<h3>Background</h3> The care for patients with lupus is complex as they may exhibit multiple concomitant medical and socioeconomic issues. To address all their needs according to the current guidelines a daunting task in busy outpatient practices. However, incorporating quality indicators patient has been found decrease mortality morbidity, improve satisfaction, reduce costs. of following recommendations from published guidelines, ACR, EULAR, we embarked on comprehensive improvement project...