Immune proteomic associations with indices of cortical development in 5-year-old children

The immune system has emerged as a critical factor influencing neurodevelopment in offspring. While this is increasingly well-studied in the context of maternal immune activation (MIA), the relationship between postnatal immune activation and brain development in childhood is far less studied. In the current study, we performed targeted immune proteomics to analyse 356 inflammation-associated proteins and examine whether peripheral immune physiology is associated with multimodal neuroimaging metrics, brain growth centiles, and cortical microstructure, in 5-year-old children. We included 101 typically developing children with immune proteomics and multimodal neuroimaging data covering structural and diffusion-weighted magnetic resonance imaging (MRI) that was modelled with FSL's linked independent component analysis (FLICA) to yield 10 multimodal brain components. For a subset of the analyses utilising immune proteomics and structural brain growth centile data, the sample size was 126 children. We observed consistent negative associations between serum immune proteins and both grey matter volume growth and global cortical thickness; for the latter, associations were statistically significant after false discovery rate correction for CXCL10, IL17A, and LILRB4. Similarly, many immune proteins were associated with increased mean diffusivity across the cortex, most notably LAMP3, NCR1, SIGLEC1, FASLG, and CXCL10 in the right medial orbitofrontal cortex. Collectively, these findings provide the first characterisation of the relationship between immune physiology and brain structure in children, and demonstrate notable associations with global cerebrocortical development. This should be extended by future studies with larger samples and multiple sampling.