Work

Early-life epigenetic programming of autoimmune diseases: what is unique to type 1 diabetes

Year: 2026

Type: article

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.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1946981

Authors: Shamila D. Alipoor, Julia Åkesson, Johnny Ludvigsson

Institutions: Linköping University, Linköping University Hospital

Language: English

Topic: Diabetes and associated disorders

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801