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Multi-modal single-cell sequencing identifies cellular immunophenotypes associated with juvenile dermatomyositis disease activity

ABSTRACT: Multi-modal single-cell sequencing identifies cellular immunophenotypes associated with juvenile dermatomyositis disease activity

PROVIDER: PRJNA787953 | ENA |

REPOSITORIES: ENA

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Multi-modal single-cell sequencing identifies cellular immunophenotypes associated with juvenile dermatomyositis disease activity

2022-04-30 | GSE190684 | GEO

Multi-Modal Single-Cell Sequencing Identifies Cellular Immunophenotypes Associated With Juvenile Dermatomyositis Disease Activity.

Project description:Juvenile dermatomyositis (JDM) is a rare autoimmune condition with insufficient biomarkers and treatments, in part, due to incomplete knowledge of the cell types mediating disease. We investigated immunophenotypes and cell-specific genes associated with disease activity using multiplexed RNA and protein single-cell sequencing applied to PBMCs from 4 treatment-naïve JDM (TN-JDM) subjects at baseline, 2, 4, and 6 months post-treatment and 4 subjects with inactive disease on treatment. Analysis of 55,564 cells revealed separate clustering of TN-JDM cells within monocyte, NK, CD8+ effector T and naïve B populations. The proportion of CD16+ monocytes was reduced in TN-JDM, and naïve B cells and CD4+ Tregs were expanded. Cell-type differential gene expression analysis and hierarchical clustering identified a pan-cell-type IFN gene signature over-expressed in TN-JDM in all cell types and correlated with disease activity most strongly in cytotoxic cell types. TN-JDM CD16+ monocytes expressed the highest IFN gene score and were highly skewed toward an inflammatory and antigen-presenting phenotype at both the transcriptomic and proteomic levels. A transitional B cell population with a distinct transcriptomic signature was expanded in TN-JDM and characterized by higher CD24 and CD5 proteins and less CD39, an immunoregulatory protein. This data provides new insights into JDM immune dysregulation at cellular resolution and serves as a novel resource for myositis investigators.

| S-EPMC9254730 | biostudies-literature

RNA-Seq of CD19+ B-cell populations from patients with juvenile dermatomyositis and controls

Project description:RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.

2019-01-03 | E-MTAB-5616 | biostudies-arrayexpress

RNA-Seq of CD19+ B-cell, CD14+ monocyte, CD4+ and CD8+ T cell populations from patients with juvenile dermatomyositis and controls

Project description:RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells, moncytes and T-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.

2022-12-31 | GSE221091 | GEO

Skeletal muscles of untreated children with juvenile dermatomyositis

Project description:Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results: Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodeling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes--HLA-DQA1, smooth muscle myosin heavy chain, clustering, plexin D1 and tenomodulin--were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusions: We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology. Keywords: Disease progression; time course

2008-07-18 | GSE11971 | GEO

dermatomyositis

Project description:muscle biopsies of normal and dermatomyositis patients Keywords: other

2004-10-01 | GSE1551 | GEO

dermatomyositis

Project description:muscle biopsies of normal and dermatomyositis patients

2007-08-03 | E-GEOD-1551 | biostudies-arrayexpress

RNA-Seq of CD19+ B-cell populations from patients with juvenile dermatomyositis and controls

Project description:RNA-Seq of CD19+ B-cell populations from patients with juvenile dermatomyositis and controls

| PRJEB20137 | ENA

Transcriptomic profiling of dermatomyositis lesions.

Project description:The microarray experiment was employed to evaluate the gene expressions in skin lesions of dermatomyositis and healthy controls.

2020-04-06 | GSE142807 | GEO

Clues to Drivers of Juvenile Dermatomyositis: Genetic Alterations after Type I Interferon and JAK Inhibitor Treatment in Pediatric Bioengineered Skeletal Muscle

Project description:To better understand the pathogenesis of juvenile dermatomyositis (JDM) we examined the genetic alterations that result from exogenous IFN I exposure in pediatric skeletal muscle. We compared untreated healthy pediatric donor-derived myobundles with those treated with IFN I as well as with JAKi baricitinib and tofacitinib. We used bulk mRNA sequencing to evaluate how IFN I and treatment with JAKi influence healthy and JDM skeletal muscle gene expression and show IFNβ leads to a greater pro-inflammatory gene response than IFNα in pediatric skeletal muscle. As a type I interferon gene signature is established in JDM, downregulated oxidative phosphorylation, myogenesis, and contractile protein gene expression is implicated in JDM pathology. These genetic changes are partially reversed by JAK inhibitors, baricitinib and tofacitinib, with baricitinib leading to greater genetic alteration than tofacitinib. Our findings show that analysis of differential gene expression in bioengineered pediatric skeletal muscle can inform our knowledge of JDM pathogenesis and therapeutic effects.

2024-09-18 | GSE243339 | GEO

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