Immune and Autoimmune Mechanisms in Autism Spectrum Disorder: Linking Molecular Pathways to Neuropsychological Trajectories Across the Lifespan

Int J Mol Sci. 2026 Sep 21;27(18):8407. doi: 10.3390/ijms27188407.

ABSTRACT

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with wide differences in cognitive, behavioral, and adaptive outcomes across the lifespan. Current evidence suggests that part of this heterogeneity may be related to interactions among genetic susceptibility, environmental exposures, and immune processes acting during important periods of brain development. This narrative review examines the molecular and cellular mechanisms through which immune dysregulation and autoimmunity may contribute to neurodevelopmental variability in ASD. It also explores possible links with age-related neuropsychological trajectories. Main topics include maternal immune activation, maternal brain-reactive autoantibodies, cytokine signaling, peripheral immune cell changes, microglial and astrocytic function, complement-mediated synaptic remodeling, and gut-immune-brain pathways. These mechanisms are discussed in relation to language, attention, executive functions, sensory processing, social cognition, emotional regulation, adaptive functioning, and psychiatric comorbidity from childhood to adulthood. Current evidence supports immune dysfunction as a possible modifier of ASD phenotypes rather than a universal or isolated cause. Direct longitudinal evidence linking specific immune profiles to defined neuropsychological trajectories is still limited, especially in adults. Integrating molecular, immunological, and neuropsychological data may help identify biologically meaningful ASD subgroups and support future biomarker development, developmental stratification, and more personalized therapeutic approaches.

PMID:42794832 | DOI:10.3390/ijms27188407