Dataset Information

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes.

ABSTRACT: Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses 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 progressed to type 1 diabetes, in comparison to autoantibody negative children.

SUBMITTER: Hirvonen MK

PROVIDER: S-EPMC10518308 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes.

Hirvonen M Karoliina MK Lietzén Niina N Moulder Robert R Bhosale Santosh D SD Koskenniemi Jaakko J Vähä-Mäkilä Mari M Nurmio Mirja M Orešič Matej M Ilonen Jorma J Toppari Jorma J Veijola Riitta R Hyöty Heikki H Lähdesmäki Harri H Knip Mikael M Cheng Lu L Lahesmaa Riitta R

Scientific reports 20230924 1

Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n ...[more]

PMID: 37743383

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.

Project description:Aims/hypothesisType 1 diabetes is an autoimmune disorder that is characterised by destruction of pancreatic beta cells by autoreactive T lymphocytes. Although islet autoantibodies (AAb) are an indicator of disease progression, specific immune biomarkers that can be used as target molecules to halt development of type 1 diabetes have not been discovered. Soluble immune checkpoint molecules (sICM) play a pivotal role in counteracting excessive lymphocyte responses, but their role in type 1 diabetes is unexplored. In this longitudinal study, we measured sICM levels in AAb-positive (AAb+) children to identify molecules related to type 1 diabetes progression.MethodsWe measured the levels of 14 sICM in the sera of AAb+ children (n=57) compared to those with recent-onset type 1 diabetes (n=79) and healthy children (n=44), obtained from two cohorts. AAb+ children were followed up and divided based on their progression to type 1 diabetes (AAbP) or not (AAbNP) (if they lost islet autoimmunity and did not develop disease in subsequent years). sICM were also measured in the sample taken at the visit closest to disease onset in AAbP children.ResultsWe found that AAb+ children had a distinct sICM profile compared with healthy children and those with recent-onset type 1 diabetes. In addition, AAb+ children who progressed to type 1 diabetes (AAbP) had higher sICM concentrations than non-progressors (AAbNP). Further, sICM levels decreased in AAbP children close to disease onset. Application of Cox regression models highlighted that high concentrations of soluble programmed cell death protein 1 (sPD-1) are associated with type 1 diabetes progression (HR 1.71; 95% CI 1.16, 2.51; p=0.007).Conclusions/interpretationThis study reveals an sICM profile that is dysregulated during the preclinical stage of type 1 diabetes, and identifies sPD-1 as a pathophysiologically-relevant molecule that is associated with disease progression, offering a potential target for early interventions in autoimmune diabetes.

Dataset Information

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes.

Publications

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets