A5028253626- Systemic Lupus Erythematosus Research
- Cytokine Signaling Pathways and Interactions
- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
- Psoriasis: Treatment and Pathogenesis
- Long-Term Effects of COVID-19
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Reproductive System and Pregnancy
- Dermatology and Skin Diseases
- Immune Cell Function and Interaction
- Fibromyalgia and Chronic Fatigue Syndrome Research
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Renal Diseases and Glomerulopathies
- Rheumatoid Arthritis Research and Therapies
- Protein Tyrosine Phosphatases
- IL-33, ST2, and ILC Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- interferon and immune responses
- Histone Deacetylase Inhibitors Research
- Computational Drug Discovery Methods
- Erythropoietin and Anemia Treatment
- Lipid metabolism and disorders
Ampel BioSolutions (United States)
2016-2025
Health First
2024
Institute of Bioinformatics
2023
Charlottesville Medical Research
2020-2022
SARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to has not yet been fully delineated, hampering precise approach therapy. To address this, we carried out comprehensive analysis gene expression data from blood, lung, airway patients. Our results indicate that pathogenesis driven by populations myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. relative absence...
Systemic lupus erythematosus (SLE) is characterized by abnormalities in B cell and T function, but the role of disturbances activation status macrophages (Mϕ) has not been well described human patients. To address this, gene expression profiles from isolated lymphoid myeloid populations were analyzed to identify differentially expressed (DE) genes between healthy controls patients with either inactive or active SLE. While hundreds DE identified cells SLE patients, there no found compared...
Abstract A role for interferon (IFN) in systemic lupus erythematosus (SLE) pathogenesis is inferred from the prominent IFN gene signature (IGS), but major species and its relationship to disease activity are unknown. bioinformatic approach employing individual signatures interrogate SLE microarray datasets demonstrates a putative numerous species, with expression of IFNB1 IFNW signatures. In contrast other SLE-affected organs, IGS less nephritis. patients active inactive have readily...
Iberdomide is a cereblon E3-ligase modulator that promotes proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) was shown to be efficacious among subjects with generalised systemic lupus erythematosus (SLE). This study sought identify baseline gene expression profiles SLE responsive iberdomide analyse impact this agent on expression. Whole blood samples obtained from 276 female in phase 2b trial (NCT03161483) were assessed by RNA sequencing followed set...
Abstract The integration of gene expression data to predict systemic lupus erythematosus (SLE) disease activity is a significant challenge because the high degree heterogeneity among patients and study cohorts, especially those collected on different microarray platforms. Here we deployed machine learning approaches integrate from three SLE sets used it classify as having active or inactive characterized by standard clinical composite outcome measures. Both raw whole blood informative...
Gene expression signatures can stratify patients with heterogeneous diseases, such as systemic lupus erythematosus (SLE), yet understanding the contributions of ancestral background to this heterogeneity is not well understood. We hypothesized that ancestry would significantly influence gene and measured 34 modules in 1566 SLE African (AA), European (EA), or Native American (NAA). Healthy subject ancestry-specific provided transcriptomic upon which patient were built. Although standard...
Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and rheumatoid arthritis (RA) are chronic inflammatory in which abnormalities of B cell function play a central role. Although it is widely accepted that autoimmune cells hyperactive vivo, full understanding their functional status AID has not been delineated. Here, we present detailed analysis the capabilities dissect mechanisms underlying altered function. Upon BCR activation, decreased...
Analysis of gene expression from cutaneous lupus erythematosus, psoriasis, atopic dermatitis, and systemic sclerosis using set variation analysis (GSVA) revealed that lesional samples each condition had unique features, but all four diseases displayed common enrichment in multiple inflammatory signatures. These findings were confirmed by both classification regression tree machine learning (ML) models. Nonlesional disease also differed normal other ML. Notably, the features used nonlesional...
Autoimmune diseases, such as systemic lupus erythematosus, are characterized by excessive inflammation in response to self-antigens. Loss of appropriate immunoregulatory mechanisms contribute disease exacerbation. We previously showed the suppressive effect vancomycin treatment during "active-disease" stage lupus. In this study, we sought understand same given before onset. To develop a model which test regulatory role gut microbiota modifying autoimmunity, treated lupus-prone mice with...
Autoantibody production by plasma cells (PCs) plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). The molecular pathways which B become pathogenic PC secreting autoantibodies SLE are incompletely characterized. Histone deactylase 6 (HDAC6) is unique cytoplasmic HDAC that modifies interaction number tubulin- associated proteins; inhibition HDAC6 has been shown to be beneficial murine models SLE, but downstream accounting for therapeutic benefit have not clearly...
To compare lupus pathogenesis in disparate tissues, we analyzed gene expression profiles of human discoid erythematosus (DLE) and nephritis (LN). We found common increases myeloid cell-defining sets decreases genes controlling glucose lipid metabolism lupus-affected skin kidney. Regression models DLE indicated increased glycolysis was correlated with keratinocyte, endothelial, inflammatory cell transcripts, decreased tricarboxylic (TCA) cycle were the keratinocyte signature. In LN,...
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of low-density granulocytes (LDGs) with a heightened capacity for spontaneous NETosis, but contribution LDGs to SLE pathogenesis remains unclear. To characterize in human SLE, gene expression profiles derived from isolated were weighted coexpression network analysis, and 92-gene module was identified. The LDG signature enriched genes related neutrophil degranulation cell cycle regulation. This assessed...
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies predominantly to nuclear material. Many aspects pathology are mediated deposition nucleic acid containing immune complexes, which also induce type 1interferon response, characteristic feature SLE. Notably, SLE remarkably heterogeneous, with variety organs involved in different individuals, who show variation severity related their ancestries. Here, we probed one potential...
Abstract Background Systemic lupus erythematosus (SLE) is known to be clinically heterogeneous. Previous efforts characterize subsets of SLE patients based on gene expression analysis have not been reproduced because small sample sizes or technical problems. The aim this study was develop a robust patient stratification system using profiling individual patients. Methods We employed set variation (GSVA) informative modules identify molecular endotypes patients, machine learning (ML) classify...
A distinct B cell population marked by elevated CD11c expression is found in patients with systemic lupus erythematosus (SLE). Cells a similar phenotype have been described during chronic infection, but variable gating strategies and nomenclature led to uncertainty of their relationship each other. We isolated hi cells from peripheral blood characterized them using transcriptome IgH repertoire analyses. Gene data revealed the IgD + − subsets were highly other, naive, memory, plasma subsets....
Objective We previously described a classification system of persons with SLE based on whole blood RNA profiles and random forest (RF) algorithm to predict individual patient endotypes. Here, we apply this prospectively in an independent set patients validate its use as staging biomarker. Methods Whole from 101 participating three clinical trials ( NCT03626311 , NCT03180021 NCT05845593 ) meeting American College Rheumatology (ACR) or Systemic Lupus Collaborating Clinics (SLICC) criteria for...
PV180 / #508 Poster Topic: AS20 - Precision Medicine Background/Purpose We previously described a classification system of persons with SLE based on whole blood (WB) mRNA profiles and random forest (RF) algorithm to predict individual patient endotypes.[1] Here, we apply this prospectively in an independent set patients validate its use as staging biomarker. Methods WB from 101 participating 3 clinical trials meeting ACR or SLICC criteria for was obtained at baseline, RNA isolated sequenced....
O058 / #380 Topic: AS12 - Genetics, Epigenetics, Transcriptomics ABSTRACT CONCURRENT SESSION 10: INTEGRATING PROTEOMIC & TRANSCRIPTOMICS IN SLE 24-05-2025 10:40 AM 11:40 Background/Purpose Current clinical methods to diagnose and evaluate the severity of lupus nephritis (LN) rely on identification kidney dysfunction followed by invasive biopsies. Here, we sought identify molecular profiles LN in tissue that would be reflected blood gene expression. Methods Gene expression was analyzed...
The persistent impact of the COVID-19 pandemic and heterogeneity in disease manifestations point to a need for innovative approaches identify drivers immune pathology predict whether infected patients will present with mild/moderate or severe disease. We have developed novel iterative machine learning pipeline that utilizes gene enrichment profiles from blood transcriptome data stratify based on severity differentiate COVID cases other acute hypoxic respiratory failure. pattern module...
Abstract Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in AsA population remain unclear. Here, we utilized available gene expression data genotype based on all non-HLA SNP associations EA patients...
Abstract Arthritis is a common manifestation of systemic lupus erythematosus (SLE) yet understanding the underlying pathogenic mechanisms remains incomplete. We, therefore, interrogated gene expression profiles SLE synovium to gain insight into nature arthritis (LA), using osteoarthritis (OA) and rheumatoid (RA) as comparators. Knee synovia from SLE, OA, RA patients were analyzed for differentially expressed genes (DEGs) also by Weighted Gene Co-expression Network Analysis (WGCNA) identify...
Objective To character the molecular landscape of patients with type 1 and 2 SLE by analysing gene expression profiles from peripheral blood. Methods Full transcriptomic RNA sequencing was carried out on whole blood samples 18 subjects selected presence manifestations typical SLE. The top 5000 row variance genes were analysed Multiscale Embedded Gene Co-expression Network Analysis to generate co-expression modules that functionally annotated correlated various demographic traits, clinical...
Abstract Regulation of intron retention (IR), a form alternative splicing, is newly recognized checkpoint in gene expression. Since there are numerous abnormalities expression the prototypic autoimmune disease systemic lupus erythematosus (SLE), we sought to determine whether IR was intact patients with this disease. We, therefore, studied global and patterns lymphocytes SLE patients. We analyzed RNA-seq data from peripheral blood T cell samples 14 suffering (SLE) 4 healthy controls second,...