Early-life epigenetic programming of autoimmune diseases: what is unique to type 1 diabetes
4 affiliations
- 1Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University
- 2Division of Bioinformatics, Department of Physics, Chemistry and Biology, Linköping University
- 3PredictMe AB
- 4Crown Princess Victoria Children’s Hospital, Linköping University Hospital
Abstract
Introduction: Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive pancreatic β-cell destruction, yet molecular features distinguishing it from other autoimmune conditions in early life remain poorly defined. We previously identified neonatal proteomic signatures predicting future T1D years before diagnosis, suggesting immune and tissue-remodeling pathways are already perturbed at birth. However, whether these alterations reflect a general autoimmune predisposition or are specific to T1D has remained unclear.
Method: To address this, we integrated cord blood DNA methylation profiles with neonatal serum proteomic data from the All Babies in Southeast Sweden (ABIS) cohort and compared T1D with other autoimmune diseases except T1D (NT1D).
Result: In an exploratory analyse, we observed a distinct early-life molecular pattern in T1D, most consistently characterized by dysregulation of β-cell metabolic genes and a CD40-centered co-stimulatory immune signal. Several components of a previously reported neonatal proteomic signature of future T1D were re-evaluated in the context of NT1D. HLA-related antigen presentation and related immune-activation signals recurred in the NT1D associated networks as well, suggesting these largely reflect broader autoimmune biology, whereas co-stimulatory signaling (CD40) and β-cell metabolic pathways showed stronger representation in T1D-associated analyses. In contrast, the NT1D profile was characterized predominantly by broader interferon-γ-associated and chemokine-driven inflammatory signaling.
Conclusion: These findings identify an exploratory early-life 43,epigenetic–proteomic pattern in T1D that combines immune and β-cell-related metabolic features, while also highlighting molecular signals that may be shared with other autoimmune conditions. These observations support further investigation of early-life molecular differences between T1D and other autoimmune diseases in larger, independent cohort.
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BibTeX
@article{alipoor2026earlylife,
title = {{Early-life epigenetic programming of autoimmune diseases: what is unique to type 1 diabetes}},
author = {Shamila D. Alipoor and Julia Åkesson and Johnny Ludvigsson},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1946981},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1946981/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Early-life epigenetic programming of autoimmune diseases: what is unique to type 1 diabetes
AU - Shamila D. Alipoor
AU - Julia Åkesson
AU - Johnny Ludvigsson
PY - 2026
DA - 2026/10/21
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1946981
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1946981/full
AB - Introduction: Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive pancreatic β-cell destruction, yet molecular features distinguishing it from other autoimmune conditions in early life remain poorly defined. We previously identified neonatal proteomic signatures predicting future T1D years before diagnosis, suggesting immune and tissue-remodeling pathways are already perturbed at birth. However, whether these alterations reflect a general autoimmune predisposition or are specific to T1D has remained unclear. Method: To address this, we integrated cord blood DNA methylation profiles with neonatal serum proteomic data from the All Babies in Southeast Sweden (ABIS) cohort and compared T1D with other autoimmune diseases except T1D (NT1D). Result: In an exploratory analyse, we observed a distinct early-life molecular pattern in T1D, most consistently characterized by dysregulation of β-cell metabolic genes and a CD40-centered co-stimulatory immune signal. Several components of a previously reported neonatal proteomic signature of future T1D were re-evaluated in the context of NT1D. HLA-related antigen presentation and related immune-activation signals recurred in the NT1D associated networks as well, suggesting these largely reflect broader autoimmune biology, whereas co-stimulatory signaling (CD40) and β-cell metabolic pathways showed stronger representation in T1D-associated analyses. In contrast, the NT1D profile was characterized predominantly by broader interferon-γ-associated and chemokine-driven inflammatory signaling. Conclusion: These findings identify an exploratory early-life 43,epigenetic–proteomic pattern in T1D that combines immune and β-cell-related metabolic features, while also highlighting molecular signals that may be shared with other autoimmune conditions. These observations support further investigation of early-life molecular differences between T1D and other autoimmune diseases in larger, independent cohort.
SN - 1664-3224
ER -