Immune proteomic associations with indices of cortical development in 5‐year‐old children
Open Access
- 10 September 2026
- journal article
- Published by Wiley in Journal of Anatomy
Abstract
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.Keywords
Funding Information
- Juho Vainion Säätiö
- Emil Aaltosen Säätiö
- Alfred Kordelinin Säätiö
- Sigrid Juséliuksen Säätiö
- Signe ja Ane Gyllenbergin Säätiö
- Orionin Tutkimussäätiö
- Strategic Research Council (#352648)
- Strategic Research Council (#352655)
- Suomen Kulttuurirahasto
- Research Council of Finland (#314390)
- Research Council of Finland (#332444)
This publication has 38 references indexed in Scilit:
- Understanding the pleiotropic effects of CXCL10/IP-10 in the immunopathogenesis of inflammatory rheumatic diseases: Implications for better understanding disease mechanismsInternational Immunopharmacology, 2025
- Sex-specific associations between maternal prenatal inflammation and offspring cortical morphology in youth: A harmonised study across four birth cohortsBrain, Behavior, and Immunity, 2024
- Test–retest reliability of diffusion tensor imaging scalars in 5‐year‐oldsHuman Brain Mapping, 2022
- The long-term impact of elevated C-reactive protein levels during pregnancy on brain morphology in late childhoodBrain, Behavior, and Immunity, 2022
- Role of IL-6 in the regulation of neuronal development, survival and functionCytokine, 2021
- Multiple Postnatal Infections in Newborns Born Preterm Predict Delayed Maturation of Motor Pathways at Term-Equivalent Age with Poorer Motor Outcomes at 3 YearsThe Journal of Pediatrics, 2018
- Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of AgeBiological Psychiatry, 2018
- The placental interleukin-6 signaling controls fetal brain development and behaviorBrain, Behavior, and Immunity, 2017
- Inflammatory biomarkers and academic performance in youth. The UP & DOWN StudyBrain, Behavior, and Immunity, 2016
- CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implicationsCytokine & Growth Factor Reviews, 2011