Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcription profiling by array of human Graves disease short and long course samples

ABSTRACT: In common with other autoimmune thyroid disorders (AITD), Gravesï¾? disease (GD) is a chronic autoimmune process. One salient feature of AITD is the inappropriate expression of HLA and other immune response molecules by thyroid follicular cells (TFC) this leading to postulate that stimuli generated in situ in the thyroid gland may contribute to trigger or perpetuate AITD. To identify the factors that determine chronicity, genes expression profiles of 2 normal and 6 autoimmune thyroid glands grouped according the course of disease (short course (SC) < 30 months, and long course (LC) > 30) were compared using Affymetrix Human Genome U133 Plus 2.0 Arrays followed by software aided pathway analysis and immunohistological studies. The results yielded over 200 differentially expressed (DE) genes pertaining to the immune system (Gene Ontology), of them nearly half of the DE genes were IFN-regulated. In all GD cases there was a predominance of genes of the humoral response and of antigen processing and presentation. While among chronicity genes, identified by a profile based algorithm, antigen presentation, viral response and chemokine genes ranked first.

ORGANISM(S): Homo sapiens

DISEASE(S): Control

SUBMITTER: Marta Ruiz Riol

PROVIDER: E-MEXP-2612 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Microarray profile of CD19+ B cells from Graves' disease patients reveals potential molecular mechanisms associated with the proliferation of B cell

Project description:Hyperthyroidism is a kind of common autoimmune disease. It is widely accepted that B lymphocytes play a significant role in GD as they are the source of autoantibodies (TRAb) against the thyroid-stimulating hormone receptor (TSHR). We previously observed B cells infiltrated in the thyroid tissue from GD patients was significantly higher than that in healthy controls.In this study, our flow cytometry results indicated that the proportion of B cells in GD patients is much higher than that in control. To explore the underlying pathological function of B cells in GD, a microarray profiles was performed in these isolated B cells.

2019-09-02 | GSE136709 | GEO

Epigenetic profiling in CD4 and CD8 T cells from Gravesâ?? disease patients reveals changes in genes associated with T cell receptor signaling [ChIP-seq]

Project description:In Gravesâ?? disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with the active chromatin histone modifications as we found decreased signals of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients. Individuals were recruited from the Estonian Genome Center of the University of Tartu. Genomic DNA was extracted from sorted CD4+ (H3K4me3 ChIP: 15 controls and 14 GD patients; H3K27ac ChIP: 11 controls and 13 GD patients) and CD8+ (H3K4me3 ChIP: 17 controls and 14 GD patients; H3K27ac ChIP: 15 controls and 14 GD patients) T cells. The data collection was performed at the SNP&SEQ Technology Platform in Uppsala University, and data analysis was done at the Institute of Biomedicine and Translational Medicine in the University of Tartu.

2015-11-06 | E-GEOD-71952 | biostudies-arrayexpress

RNA-Seq of IL-2-KO follicular CD8 T cells and IL-2-KO follicular CD4 T cells

Project description:Follicular CXCR5+ PD-1+ CD8 T cells (CD8 Tfc) arise in multiple models of systemic autoimmunity yet their functional contribution to disease remains in debate. Here we define the follicular localization and functional interactions of CD8 Tfc with B cells during autoimmune disease. The absence of functional T regulatory cells in autoimmunity allows for CD8 Tfc development that then expands with lymphoproliferation. CD8 Tfc are identifiable within the lymph nodes and spleen during systemic autoimmunity, but not during tissue-restricted autoimmune disease. Autoimmune CD8 Tfc cells are polyfunctional, producing helper cytokines IL-21, IL-4, and IFNγ while maintaining cytolytic proteins CD107a, granzyme B, and TNF. During autoimmune disease, IL-2-KO CD8 T cells infiltrate the B cell follicle and germinal center, including the dark zone, to induce AID in vitro in naïve B cells via IL-4 secretion. CD8 Tfc represent a unique CD8 T cell population with a diverse effector cytokine repertoire that can contribute to pathogenic autoimmune B cell response.

2022-01-22 | GSE177911 | GEO

Epigenetic profiling in CD4 and CD8 T cells from Gravesâ disease patients reveals changes in genes associated with T cell receptor signaling [gene expression]

Project description:In Gravesâ disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with the active chromatin histone modifications as we found decreased signals of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients. Individuals were recruited from the Estonian Genome Center of the University of Tartu. Total RNA was extracted from sorted CD4+ (10 controls and 15 GD patients) and CD8+ (8 controls and 16 GD patients) T cells. The data collection was performed at the Estonian Genome Center Core Facility, and data analyses was done at the Institute of Biomedicine and Translational Medicine in the University of Tartu.

2015-11-06 | E-GEOD-71956 | biostudies-arrayexpress

Epigenetic profiling in CD4 and CD8 T cells from Gravesâ disease patients reveals changes in genes associated with T cell receptor signaling [methylation]

Project description:In Gravesâ disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with the active chromatin histone modifications as we found decreased signals of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients. Individuals were recruited from the Estonian Genome Center of the University of Tartu. Genomic DNA was extracted from sorted CD4+ (31 controls and 36 GD patients) and CD8+ (31 controls and 37 GD patients) T cells. The data collection was performed at the SNP&SEQ Technology Platform in Uppsala University, and data analysis was done at the Institute of Biomedicine and Translational Medicine in the University of Tartu.

2015-11-06 | E-GEOD-71955 | biostudies-arrayexpress

Genetically-driven target tissue over-expression of CD40: A novel mechanism in autoimmune disease

Project description:The CD40 gene, an important immune regulatory gene, is also expressed and functional on non-myeloid derived cells, many of which are targets for tissue specific autoimmune diseases, including d thyroid follicular cells in Graves’ disease (GD). Whether target tissue CD40 expression plays a role in autoimmune disease etiology has yet to be determined. Here we show for the first time, that target-tissue over-expression of CD40 plays a key role in the etiology of autoimmunity. Using a murine model of GD, we demonstrated that thyroidal CD40 over-expression augmented the production of thyroid specific antibodies, resulting in more severe experimental autoimmune Graves’ disease (EAGD), whereas deletion of thyroidal CD40 suppressed disease. Using transcriptome and immune-pathway analyses we showed that in both EAGD mouse thyroids and human primary thyrocytes, CD40 mediates this effect by activating downstream cytokines and chemokines, most notably IL-6. To translate these findings into therapy, we blocked IL-6 during EAGD induction in the setting of thyroidal CD40 over-expression, and showed decreased levels of TSHR stimulating antibodies and frequency of disease. We conclude that target tissue over-expression of CD40 plays a key role in the etiology of organ specific autoimmune disease. CD40 in Thyroid Autoimmunity: 1) Incubation of human thyroid cells with G28.5, a CD40 stimulating antibody, and purification of RNA, conversion to cDNA, measurement of mRNA expression using RNAseq. 2) Removal of thyroid tissues from CD40 over-expressing transgenic mice and wild type mice, purification of RNA, conversion to cDNA measurement of mRNA expression using RNAseq.

2012-10-03 | E-GEOD-39081 | biostudies-arrayexpress

Epigenetic profiling in CD4 and CD8 T cells from Graves’ disease patients reveals changes in genes associated with T cell receptor signaling [gene expression]

Project description:In Graves’ disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with the active chromatin histone modifications as we found decreased signals of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients.

2015-11-06 | GSE71956 | GEO