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Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells [TCR-Seq]

ABSTRACT: Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells [TCR-Seq]

PROVIDER: PRJNA986871 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25006633_1.fastq.gz	Fastqsanger.gz
	SRR25006633_2.fastq.gz	Fastqsanger.gz
	SRR25006634_1.fastq.gz	Fastqsanger.gz
	SRR25006634_2.fastq.gz	Fastqsanger.gz
	SRR25006635_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells [TCR-Seq]

Project description:The endocrine pancreas is one of the most inaccessible organs of the human body. Its autoimmune attack leads to type 1 diabetes (T1D) in a genetically susceptible population and a lifelong need for exogenous insulin replacement. Monitoring disease progression by sampling peripheral blood would provide key insights into T1D immune-mediated mechanisms and potentially change preclinical diagnosis and the evaluation of therapeutic interventions. This effort has been limited to the measurement of circulating anti-islet antibodies, which despite a recognized diagnostic value, remain poorly predictive at the individual level for a fundamentally CD4 T cell-dependent disease. Here, peptide-major histocompatibility complex tetramers were used to profile blood anti-insulin CD4 T cells in mice and human. While percentages of these were not directly informative, the state of activation of anti-insulin T cells measured by RNA and protein profiling was able to distinguish normalcy versus disease progression. Activated anti-insulin CD4 T cell were detected at time of diagnosis but also in patients with established disease and in some at-risk individuals. These results support the concept that antigen specific CD4 T cells might be used to monitor autoimmunity in real time. This advance can inform our approach to T1D diagnosis and therapeutic interventions in the pre-clinical phase of anti-islet autoimmunity.

2023-07-06 | GSE235666 | GEO

Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells

Project description:Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells

| PRJNA986866 | ENA

Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells [Fluidigm]

Project description:Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells [Fluidigm]

| PRJNA984640 | ENA

Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells [Fluidigm]

2023-07-06 | GSE235123 | GEO

Stool metaproteomics of children with islet autoimmunity

Project description:The gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms. Here, we apply an integrative approach to combine comprehensive faecal virome, microbiome and metaproteome data sampled before and at the onset of islet autoimmunity in 40 children. We show strong age and antibody related effects across the datasets. Mastadenovirus infection was associated with profound functional changes in the faecal metaproteome. Multiomic factor analysis modelling revealed proteins associated with carbohydrate transport from the genus Faecalibacterium were associated with islet autoimmunity. These findings demonstrate functional remodelling of the gut microbiota accompanies both islet autoimmunity and viral infection.

2022-08-22 | PXD032997 | Pride

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Project description:<h4><strong>AIMS/HYPOTHESIS: </strong>Metabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group.</h4><h4><strong>METHODS: </strong>We analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS.</h4><h4><strong>RESULTS: </strong>In early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.</h4><h4><strong>CONCLUSIONS/INTERPRETATION: </strong>Our findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.</h4>

2022-01-19 | MTBLS802 | MetaboLights

The anti-inflammatory IL-1 receptor antagonist (IL-1ra) protects against the development of islet autoimmunity.

Project description:Through gene expression profiling in cultured lymphocytes and PBMCs from a large set of T1D patients and controls, we demonstrate that IL-1ra may protect against the development of islet autoimmunity and T1D through down-regulating a large number of inflammatory genes and pathways. Keywords: autoimmunity; IL-1Ra;Type 1 diabetes (T1D)

2012-12-01 | GSE14368 | GEO

APMAT analysis reveals associations between antigen-TCR sequences and CD8 T cell phenotype in COVID-19 patients

Project description:Here, we describe Antigen-TCR Pairing and Multiomic Analysis of T-cells (APMAT), which is an integrated experimental-computational framework designed for the high-throughput capture and analysis of antigen specific CD8 T cells, with paired antigen, TCR sequence, and transcriptome information from the same single cells, from many patient samples in parallel.

2024-09-18 | E-MTAB-14002 | biostudies-arrayexpress

Mapping T cell responses to native and neo- islet antigen epitopes in at risk and type 1 diabetes subjects

Project description:Gene expression and T cell receptor profiles from single cells from populations of T cells stimulated with islet autoantigenic peptides. CD4 T cells were stimulated with native (proinsulin, GAD fragments) or neo-antigen epitopes or flu vaccine (Pediacel). Activated cells (identified as CD19- CD3+ CD4+,CD45-RO+ CD95+, CD154+CD69+ CD27+) were FACS-sorted, barcodes for samples were introduced with cell hashing as follows: patient, 1 pool 1 (Hashtag 1); patient 1 pool 2 (Hashtag 2) patient 2 pool 1 (Hashtag 3); patient 2 pool 2 (Hashtag 4) and Pediacel (patient 1 and 2; Hashtag 5). Hashtag info in ADT files, TCR sequences provided in VDJ files.

2021-05-29 | E-MTAB-10323 | biostudies-arrayexpress

Dynamics of Plasma Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes: Type 1 Diabetes Prediction and Prevention Study (DIPP)

Project description:Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that children who progressed to islet autoimmunity or overt T1D are characterized by distinct lipidomic signatures, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.

2018-07-16 | MTBLS620 | MetaboLights

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