Biological sex impacts immune cell proportions and epigenetic profiles in the developing pediatric immune system

Age- and sex-related differences in immune cell compositions and immune outcomes have been identified across the life course, but a comprehensive and nuanced characterization of these changes during the rapid developmental window of early life is lacking. We explore immune associated DNA methylation (DNAm) changes in the context of age and sex leveraging whole blood samples collected at ages one and five from CHILD, a Canadian longitudinal pediatric cohort (n = 760: 356 female and 404 male). DNAm-based computational cell type deconvolution reveals significant changes in all estimated immune cell types across time, with notable sex differences. In addition, we identify distinct DNAm signatures reflecting age- and sex-associated immune profiles in early life. While age-related DNAm changes are relatively limited, sex-associated differences are consistent across this developmental window and partially validate in independent pediatric cohorts. Together, these findings provide insights into early immune system maturation, underscoring the presence of sex differences prior to puberty.