Maternal and Neonatal Immune Signatures at Birth and Future Type 1 Diabetes: Potential Antiviral and Inflammatory Immune Profiles

Background/Objectives: Prenatal immune programming may contribute to the development of type 1 diabetes (T1D), but the maternal and neonatal immune profiles associated with subsequent disease remain poorly understood. This study aims to investigate maternal and neonatal serum proteomic signatures and cord blood DNA methylation patterns in relation to future T1D. Methods: We analyzed maternal serum proteomic profiles collected at delivery, neonatal cord serum proteomic profiles, and cord blood DNA methylation data from mothers and children in the ABIS birth cohort. Results: After false discovery rate (FDR) correction, 60 maternal proteins, but only 3 neonatal proteins, differed significantly between the T1D and control groups. Both proteomic analyses showed enrichment of immune and inflammatory pathways, with Th1/Th2, Th17, IL-17, and chemokine signaling additionally enriched in neonatal serum. In a further analysis restricted to virus-annotated KEGG pathways, the enriched pathways in both datasets converged on shared immune and inflammatory signaling components and did not indicate infection with a specific pathogen. Network integration identified shared immune hubs, including TNF, CD40LG, and multiple CCL/CXCL chemokines. Cord blood DNA methylation changes were modest, although nominally significant differentially methylated genes (DMGs) were associated with immune-related and host–pathogen interaction pathways, showing biological convergence with the proteomic findings. Conclusion: Maternal and neonatal immune profiles at birth may reflect inflammatory processes associated with subsequent T1D development. Maternal serum proteomics provided stronger statistical evidence, whereas the neonatal findings were hypothesis-generating. Further studies in larger independent cohorts, including targeted protein assays, are needed to validate these findings and clarify their biological significance.