{
  "abstract": "Introduction Seroconversion (SV) marks islet autoimmunity (IA) onset and preclinical type 1 diabetes (T1D), yet the contributions beyond T and B lymphocytes remain unclear. We evaluated DNA methylation (DNAm)-derived immune cell ratios between T1D cases and controls around SV.Research design and methods High-resolution immune cell-type deconvolution of peripheral blood DNAm from nested case-control samples in the Diabetes Autoimmunity Study in the Young (DAISY; n=151) and the Environmental Determinants of Diabetes in the Young (TEDDY; n=166) estimated immune cell proportions at pre-SV (the latest visit before SV) and at SV (the first visit with persistent detected autoantibodies) to construct immune cell ratios, such as the neutrophil-to-lymphocyte ratio (NLR). Linear models compared T1D cases to matched T1D controls (IA negative) at pre-SV, SV, and the change across time points.Results From pre-SV to SV, controls showed expected developmental increases in B-memory/naive, B-CD4T-CD8T memory/naive, and NLR, while cases failed to follow these patterns, with attenuated trajectories of 35%, 38%, and 21%, respectively. Pre-SV, cases had 15% higher NLR and 9% lower CD4T/CD8T. At SV, the combined B-CD4T-CD8T memory/naive ratio was 26% reduced in cases.Conclusions These patterns may reflect increased neutrophil activation or pancreatic infiltration, altered CD4 and CD8 T cell balance, and delayed or disrupted immune maturation with the persistence or expansion of naive B and T cells or impaired transition to memory B and T subsets following antigen exposure. Our findings highlight early shifts in innate and adaptive immune cell dynamics during T1D pathogenesis and support methylation-derived immune cell ratios as potential biomarkers for risk stratification and mechanistic insight.",
  "authors": [
    {
      "affiliations": [
        "Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA",
        "Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, Colorado, USA"
      ],
      "name": "Kirk R Hohsfield"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA",
        "Musculoskeletal Research Center, Children’s Hospital Colorado, Aurora, Colorado, USA"
      ],
      "name": "Patrick Carry"
    },
    {
      "affiliations": [
        "Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, Colorado, USA"
      ],
      "name": "Sarah Slack"
    },
    {
      "affiliations": [
        "Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, Colorado, USA"
      ],
      "name": "Charles T Repaci"
    },
    {
      "affiliations": [
        "Division of Rheumatology, University of Colorado Anschutz, Aurora, Colorado, USA"
      ],
      "name": "Lauren A Vanderlinden"
    },
    {
      "affiliations": [
        "Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, USA"
      ],
      "name": "Katerina Kechris"
    },
    {
      "affiliations": [
        "Barbara Davis Center for Diabetes, University of Colorado Anschutz, Aurora, Colorado, USA"
      ],
      "name": "Marian Rewers"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA"
      ],
      "name": "Jill M Norris"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA",
        "Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, Colorado, USA"
      ],
      "name": "Randi K Johnson"
    }
  ],
  "title": "Differences in immune cell profiles around the time of islet autoimmunity seroconversion in children with and without type 1 diabetes",
  "uid": "0efee673-a5f7-5d24-a2a9-8ce34c5912b8"
}