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CEACAM 1, 3, 5 and 6 -positive classical monocytes correlate with interstitial lung disease in early systemic sclerosis

ABSTRACT: To clarify the characteristics of CEACAM-positive monocytes in systemic sclerosis (SSc), we performed gene expression microarrays between CEACAM-positive and CEACAM-negative classical monocytes from diffused cutaneous systemic sclerosis(dcSSc) patients. We further analyzed expression levels of each subtype of CEACAM on monocytes from dcSSc by flow cytometry and performed gene expression microarrays between CEACAM1+CEACAM6- and CEACAM1-CEACAM6+ monocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE207423 | GEO | 2022/08/29

REPOSITORIES: GEO

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CEACAM 1, 3, 5 and 6 -positive classical monocytes correlate with interstitial lung disease in early systemic sclerosis

Project description:To clarify the characteristics of CEACAM-positive monocytes in systemic sclerosis (SSc), we performed gene expression microarrays between CEACAM-positive and CEACAM-negative classical monocytes from diffused cutaneous systemic sclerosis(dcSSc) patients. We further analyzed expression levels of each subtype of CEACAM on monocytes from dcSSc by flow cytometry and performed gene expression microarrays between CEACAM1+CEACAM6- and CEACAM1-CEACAM6+ monocytes.

2022-08-29 | GSE207424 | GEO

Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis

Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation and fibrosis of the skin and internal organs. We sought to assess the clinical and molecular effects associated with response to intravenous abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).

2016-02-01 | GSE66321 | GEO

Nilotinib (Tasigna) in the Treatment of Early Diffuse Systemic Sclerosis: An Open-Label, Pilot Clinical Trial

Project description:To assess the safety, efficacy, and molecular change associated with treatment of patients with early, diffuse cutaneous systemic sclerosis (dcSSc) with nilotinib (Tasigna™). In this open-label pilot trial 6 adult patients with early dcSSc received nilotinib. Primary endpoints were safety and change in modified Rodnan Skin Score (MRSS) after 6 months. Lesional skin biopsies at baseline, 6 and 12 months of treatment were assessed by histopathology, immunohistochemistry, and DNA microarray.

2015-08-27 | E-GEOD-65405 | biostudies-arrayexpress

Nilotinib (Tasigna) in the Treatment of Early Diffuse Systemic Sclerosis: An Open-Label, Pilot Clinical Trial

2015-08-27 | GSE65405 | GEO

Transcription profiling of human skin bioposis from patients with diffuse scleroderma and limited scleroderma

Project description:RNA expression profiling was carried out for systemic sclerosis (scleroderma) on skin biopsies obtained from both diffuse scleroderma (dcSSc) and limited scleroderma (lcSSc) subjects patients and compared to normal subjects. The patient group comprised of 4 dcSSc and 2 lcSSc subjects, all of whom were Caucasian and belonged to the age range of 42-73 (Mean age = 61.6). Patient sample set consisted of 3 females and 3 males. Race matched female volunteers from the same geographical area were recruited as controls (n = 4) and belonged to the age range of 41-62 (Mean age = 52).

2015-03-25 | E-MEXP-1214 | biostudies-arrayexpress

Homo sapiens

Project description:Gene expression from human keratinocytes isolated from limited systemic sclerosis (lcSSc) and diffuse systemic sclerosis (dcSSc) skin biopsy

| PRJNA320417 | ENA

Transcriptome analysis of CD14+ monocytes from SSc patients

Project description:Purpose: To compare transcriptome profile of CD14+ blood monocytes from systemic sclerosis (SSc) patients and healthy controls. Methods: CD14+ monocytes were isolated from peripheral blood of lcSSc (n=5, age=54.4±6.7), dcSSc patients (n=5, age=51.8±7.2) and age- and sex-matched healthy controls (HC) (n=5, age=50.8±9.7). Total RNA was isolated and polyA libraries were prepared using TruSeq Stranded mRNA kit. Next Generation Sequencing was performed using Illumina HiSeq 4000 platform. Differentially expressed genes were computed using DESeq2 algorithm. Results: We detected 1440 differentially expressed genes between dcSSc vs HC and 225 between lcSSc and HC respectively (p≤0.01; log2 ratio≥0.5, Fig 1). Among those, in dcSSc 1076 were upregulated (e.g. MMP9, IL1R2, FLT3, MIF, TLR9) and 364 were downregulated (e.g. TGFBR1, CD44, CD244, HLA-DRA, HLA-G). In lcSSc 160 transcripts were upregulated (e.g. CCL2, WNT5B, MMP17) and 65 were downregulated (e.g. KLF11, IRAK2). We identified 123 commonly deregulated genes between SSc subgroups (e.g. CCL3, CD14, IL27, MMP17). Principal component analysis showed close clustering within SSc subgroups and clear separation from healthy controls. Pathway analysis revealed alterations in several biological processes important in fibrogenesis including antigen presentation, MIF-induced immune responses, TGF-β, NOTCH and WNT signalling pathways. qPCR analysis further confirmed differences in gene expression on mRNA level (n HC=8, n SSc=25, p≤0.05). Conclusions: To our knowledge, this is the first global transcriptome analysis of peripheral blood CD14+ monocytes in SSc. Our results suggest a primary activation of monocytes in peripheral blood, which might be further translated into novel cellular biomarker of the disease and potentially used for distinguishing between responders and non-responders to a novel treatment in future clinical trials.

2021-09-10 | GSE157840 | GEO

Expansion of FCGR3A+ macrophages, FCN1+ mo-DC, and plasmacytoid dendritic cells associated with severe skin disease in systemic sclerosis

Project description:We sought a comprehensive understanding of myeloid cell types driving fibrosis in diffuse cutaneous systemic sclerosis (dcSSc) skin. T-stochastic neighbor embedding analysis of single cell transcriptome data revealed 12 myeloid cell clusters, nine of which paralleled previously described HC Mφ/DC clusters and three of which were dcSSc-specific myeloid cell clusters. One SSc-associated macrophage cluster, highly expressing FCGR3A, on pseudotime analysis was suggested to derive from normal CCR1+ and MARCO+ macrophages. A second SSc-associated myeloid population, highly expressed monocyte markers: FCN1, EREG, S100A8 and S100A9, but was closely related to cDC2 on pseudotime analysis and identified as Mo-DC. Mo-DC were associated with more severe skin disease. Proliferating macrophages and plasmacytoid dendritic cells were detected almost exclusively in dcSSc skin, the latter clustering with B cells and apparently derived from lymphoid progenitors. Transcriptional signatures in these and other myeloid populations indicate innate immune activation, possibly through TLRs, and highly upregulated chemokines. However, the appearance and activation of myeloid cells is variable between patients, indicating differing underlying pathogenesis and/or temporal disease activity.

2021-08-13 | GSE181957 | GEO

Classical Monocytes from African American Patients with Systemic Sclerosis

Project description:Classical Monocytes from African American Patients with Systemic Sclerosis

| PRJNA803206 | ENA

Histone modifications underlie monocyte dysregulation in Systemic Sclerosis patients, underlining the treatment potential of epigenetic targeting [RNA-seq]

Project description:Systemic sclerosis (SSc) is a chronic autoimmune disease that mainly affects the connective tissue. Monocytes have been shown to be an important cell type involved in the pathogenesis of SSc. By performing RNA-sequencing analysis on whole RNA isolated from peripheral blood CD14+ monocytes obtained from SSc patients, together with healthy controls matched for sex and age, obtained from the University Medical Center Utrecht (definite SSc cohort), and the University of Milan (non-fibrotic SSc cohort), we aimed to characterize the transcriptomic landscape of monocytes of patients with (pre-clinical) systemic sclerosis. Moreover, ChIPseq data was available for a part of the subjects included in the RNA-seq analysis and the correlation between the histone marks and gene expression was studied. The samples used in this study are part of the SYSCLASS cohort.

2019-03-06 | GSE124073 | GEO

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