Dataset Information

Chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

ABSTRACT: Type 1 diabetes (T1D) usually has a preclinical phase identified by the presence of circulating autoantibodies to pancreatic islet antigens, and most young children who have multiple autoantibodies progress to diabetes within 10 years. While autoantibodies denote underlying islet autoimmunity, how this process is initiated and then progresses to clinical diabetes on a background of genetic susceptibility is not clearly understood. Only one study has thus far reported changes in gene expression in isolated immune cells associated with progression to islet autoimmunity. We analysed chromatin accessibility by ATAC-seq in CD4+ T cells in four genetically at-risk children with islet autoantibodies who progressed to diabetes in ≤ 3 years (‘progressors’), compared to five at-risk children matched for sex, age and HLA who had not progressed (‘non-progressors). From ATAC-seq data, we generated the first map of chromatin accessibility in T cells of islet autoantibody-positive children. Progression was associated with a subtle reconfiguration of regulatory chromatin regions, and some of the chromatin conformation changes could be linked to progression associated expression changes at cytotoxic genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE185189 | GEO | 2022/03/09

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Aims/hypothesis: Biomarkers are needed to accurately predict and monitor type 1 diabetes progression during the substantially heterogeneous presymptomatic period of the disease development. To address this concern, we studied temporal changes in the plasma and serum proteomes of < 5-year-old children with HLA-conferred risk for type 1 diabetes, by analysing longitudinal sample series that were collected at regular intervals between birth and diagnosis. Methods: Using mass spectrometry-based discovery proteomics, longitudinal sample series from children positive for multiple autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n=10) were analysed and compared with similar measurements from children, matched from age and gender who were either positive for single autoantibody (n=10) or autoantibody negative (n=10). Following analysis of the data with an additive Gaussian process regression model (LonGP), targeted proteomics was used to verify 11 biomarker candidates in a similar yet independent cohort of children who progressed to the disease within 5 years of age (n=31) and matched autoantibody negative children (n=31). Results: These data reiterated extensive age related trends for protein levels in young children. Further, by combining the utility of LonGP together with the targeted analysis in an extended cohort with more frequent sampling points, these analysis demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who later progressed to type 1 diabetes, in comparison to autoantibody negative children. Conclusions/interpretation: Through the comparative analysis of prospectively collected samples, our data indicate that the serum/plasma levels of APOC1 are decreased in islet autoantibody positive children who develop type 1 diabetes at a young age. In future studies, APOC1 could be used as an additional measurement to improve early prediction of type 1 diabetes and selection of subjects for intervention studies.

Dataset Information

Chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure