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Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["2103-05094"],"award-info":[{"award-number":["2103-05094"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2026,5,9]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research design and methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjdrc-2026-006015","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T14:30:12Z","timestamp":1779719412000},"page":"e006015","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Differences in immune cell profiles around the time of islet autoimmunity seroconversion in children with and without type 1 diabetes"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6707-7913","authenticated-orcid":false,"given":"Kirk R","family":"Hohsfield","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, 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