Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reduced CD8 T cell exhaustion in DR4 risk subjects is selectively augmented with therapy [whole blood]

ABSTRACT: Exhausted CD8 T cells (TEX) are associated with worse outcome in cancer yet better outcome in autoimmunity. However, factors contributing to reduced TEX in autoimmunity are poorly understood. We use two genetically related autoimmune diseases, type 1 diabetes (T1D) and rheumatoid arthritis (RA), to explore these factors. We identify a common human peripheral blood TIGIT+KLRG1+ CD8 TEX population: TIGIT+KLRG1+ CD8 TEX of healthy controls (HC), T1D, and rheumatoid arthritis (RA) subjects share EOMES signature genes, are increased with age and in chronic viral-specific cells and are hyporesponsive in vitro. Consistent with a genetic determinant, TIGIT+KLRG1+ TEX are stable within but vary between individuals. In HC and RA subjects (n>100/cohort), lower levels of EOMES transcriptional modules and TIGIT+KLRG1+ TEX were associated with RA HLA risk alleles (DR0401, 0404, 0405, 0408, 1001) even when considering disease status and CMV seropositivity. TIGIT+KLRG1+ TEX significantly increased in RA HLA risk but not non-risk subjects treated with abatacept (CTLA4Ig); no change in TIGIT+KLRG1+ TEX was observed with adalimumab (anti-TNF) therapy. The DR4 association and selective modulation with abatacept suggests that therapeutic modulation of TEX may be more effective in DR4 subjects and TEX may be indirectly influenced by cellular interactions that are blocked by abatacept.

ORGANISM(S): Homo sapiens

PROVIDER: GSE216678 | GEO | 2023/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Reduced CD8 T cell exhaustion in DR4 risk subjects is selectively augmented with therapy [CD8s]

Project description:Exhausted CD8 T cells (TEX) are associated with worse outcome in cancer yet better outcome in autoimmunity. However, factors contributing to reduced TEX in autoimmunity are poorly understood. We use two genetically related autoimmune diseases, type 1 diabetes (T1D) and rheumatoid arthritis (RA), to explore these factors. We identify a common human peripheral blood TIGIT+KLRG1+ CD8 TEX population: TIGIT+KLRG1+ CD8 TEX of healthy controls (HC), T1D, and rheumatoid arthritis (RA) subjects share EOMES signature genes, are increased with age and in chronic viral-specific cells and are hyporesponsive in vitro. Consistent with a genetic determinant, TIGIT+KLRG1+ TEX are stable within but vary between individuals. In HC and RA subjects (n>100/cohort), lower levels of EOMES transcriptional modules and TIGIT+KLRG1+ TEX were associated with RA HLA risk alleles (DR0401, 0404, 0405, 0408, 1001) even when considering disease status and CMV seropositivity. TIGIT+KLRG1+ TEX significantly increased in RA HLA risk but not non-risk subjects treated with abatacept (CTLA4Ig); no change in TIGIT+KLRG1+ TEX was observed with adalimumab (anti-TNF) therapy. The DR4 association and selective modulation with abatacept suggests that therapeutic modulation of TEX may be more effective in DR4 subjects and TEX may be indirectly influenced by cellular interactions that are blocked by abatacept.

2023-06-30 | GSE216679 | GEO

B lymphocyte alterations accompany abatacept resistance in new-onset type 1 diabetes

Project description:Peripheral blood samples were collected from subjects enrolled in the TrialNet study TN-09. This was a phase II study of the effects of the T cell costimulation inhibitor CTLA4-Ig (abatacept) in new-onset T1D. Total RNA was isolated from whole blood samples and then globin-reduced. RNAseq libraries were prepared from the globin-reduced RNA.

2019-02-28 | GSE124284 | GEO

Synovial biopsies of rheumatoid arthritis and healthy controls

Project description:Synovial biopsies were obtained from rheumatoid arthritis (RA) synovium and from subjects without a joint disease to find gene upregulated during RA. The promoters of genes upregulated during RA compared to HC can be used to obtain disease-regulated gene therapy.

2016-01-27 | GSE77298 | GEO

Genome-wide DNA methylation profiling of CD4+ T cells and CD19+ B cells in autoimmune-disease associated HLA class II genotype carriers (HLA-DR2-DQ6, -DR3-DQ2 and -DR4-DQ8 homozygotes) using Illumina Infinium HumanMethylation EPIC beadchip

Project description:The Human leukocyte antigen (HLA) -region, especially HLA class I and II genes, plays a major role in the predisposition to autoimmune disorders. Particularly three HLA haplotypes, DRB1*03-DQA1*05-DQB1*02 (DR3-DQ2), DRB1*04:01-DQA1*03-DQB1*03:02 (DR4-DQ8) and DRB1*15-DQA1*01-DQB1*06:02 (DR2-DQ6), have an important role in many autoimmune diseases: for example, in type 1 diabetes (T1D) the DR2-DQ6 is associated with a strongly decreased T1D risk and the DR3-DQ2 and DR4-DQ8 are associated with a moderately increased T1D risk. To clarify the mechanisms behind this association, we examined genome-wide DNA methylation in CD4+ T cells and CD19+ B cells of healthy subjects homozygous either for DR3-DQ2 (n = 19), DR4-DQ8 (n = 17) or DR2-DQ6 (n = 14), and compared methylation between the genotypes. For the study, CD4+ T cells and CD19+ B cells were isolated consecutively from PBMC samples using magnetic bead separation. DNA was extracted from the cell lysates with AllPrep DNA/RNA/miRNA Universal Kit (Qiagen, Germany). Then the individual DNA samples were pooled into 11 pooled samples with 4–5 samples per pooled sample. The original 50 samples were designated pools based on age and sex to ensure that the age and sex distributions would be as similar as possible between the pooled samples. The mean age (±SD) in the three HLA-groups (DR2-DQ6, DR3-DQ2 and DR4-DQ8) were 15.0 (±8.3), 11.1 (±5.6) and 11.8 (±7.9) and their male to female ratios were 8/6, 9/10 and 11/6. Similar pooled samples were created for both the CD4+ T cell and the CD19+ B cell samples. Then DNA methylation was examined in the pooled CD4+ T cell and CD19+ B cell samples using Illumina Infinium HumanMethylation EPIC beadchip.

2024-06-20 | E-MTAB-13654 | biostudies-arrayexpress

Gene expression profiling in Abatacept treated Rheumatoid Arthritis patients according to response

Project description:The objective of this study was to identify specific gene expression profiles able to predict the response of rheumatoid arthritis patients treated with methotrexate /abatacept (Aba). Thirty six RA patients were received Abatacept. The drug efficacy was evaluated with the DAS28 score after 6 months of treatment according to the EULAR response criteria. Among 36 Aba RA patients, 17 were responders and 19 were classified as no-responders. A blood sample was carried out in patients just before the first injection of treatment in PaxGene tubes. Two color experiments : patient(Cy5)/Control pool (Cy3).

2017-05-17 | E-GEOD-68215 | biostudies-arrayexpress

TCR sequencing analysis of islets from NOD mice on hydrolyzed casein and hydrolyzed casein + 4% gluten diets

Project description:Protein source in diet greatly influences the incidence of type-1 diabetes (T1D) in non-obese diabetic (NOD) mouse colonies. NOD mice fed a diet containing hydrolyzed casein (HC) as the sole protein source are protected from T1D. Replacing 1/5th of the HC with gluten restores high T1D to NOD mice. We hypothesized that gluten might promote inflammation in the islets. We used TCR sequencing to characterize the clonal frequency of infiltrating T cells from the pancreatic islets of Langerhans of NOD mice fed a 20% HC diet or a 16% HC + 4% gluten diet.

2023-01-04 | GSE218336 | GEO

Gene expression profiling in Abatacept treated Rheumatoid Arthritis patients according to response

2017-05-17 | GSE68215 | GEO

Transcriptional Signatures as a Disease-Specific and Predictive Inflammatory Biomarker for Type 1 Diabetes [T1D_114]

Project description:The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D and HC cohorts. In addition, we examined T1D progression by looking at longitudinal, pre-onset and longstanding T1D samples. UPN727 cells were stimulated with autologous plasma (n=7), unrelated healthy control plasma (n=44), recent onset T1D plasma (n=46), longstanding T1D plasma (n=11), or longitudinal series plasma (n=6 time points) from pre/post onset. Gene expression analysis was performed in order to evaluate the transcriptional signature associated with T1D.

2012-09-01 | E-GEOD-35725 | biostudies-arrayexpress

Single cell RNA-sequencing analysis of islets from WT NOD mice on different diets

Project description:Protein source in diet greatly influences the incidence of type-1 diabetes (T1D) in non-obese diabetic (NOD) mouse colonies. NOD mice fed a diet containing hydrolyzed casein (HC) as the sole protein source are protected from T1D. Replacing 1/5th of the HC with gluten restores high T1D to NOD mice. We hypothesized that gluten might promote inflammation in the islets. We used single cell RNA sequencing (scRNAseq) to characterize and contrast the transcriptional profiles of endocrine cells and islet infiltrating leukocytes from the pancreatic islets of Langerhans of NOD mice fed a 20% HC diet or a 16% HC + 4% gluten diet.

2023-01-04 | GSE217493 | GEO

Gene expression fluctuation in Abatacept treated Rheumatoid Arthritis patients between baseline and 6 months

Project description:The objective of this study was to identify response-specific gene expression fluctuations in methotrexate /abatacept (Aba) treated rheumatoid arthritis patients : responders (R) VS no-responders (NR). Nineteen RA patients were received Abatacept. The drug efficacy was evaluated with the DAS28 score after 6 months of treatment according to the EULAR response criteria. Among 19 Aba RA patients, 14 were R and 5 were classified as NR. A blood sample was carried out in patients both at baseline (just before the first injection of ABA) and at 6 months in PaxGene tubes.

2020-07-24 | GSE91079 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data