THE ROLE OF IMMUNE DISORDERS IN THE ETIOLOGY OF AUTISM SPECTRUM DISORDER: A SYSTEMATIC REVIEW

Abstract

Introduction: Evidence suggests that immune and neuroinflammatory axes contribute to the pathophysiology of autism spectrum disorder (ASD), although the magnitude and clinical applicability of these findings remain heterogeneous.Objective: To synthesize evidence from primary studies on immune disorders associated with ASD and assess methodological quality by study design.Methods: Systematic review registered in PROSPERO (CRD420251067439) and conducted according to PRISMA 2020. Searches were performed in PubMed/MEDLINE, SciELO, and LILACS (2020–2025), with reference list screening. Inclusion: original observational (cross-sectional/cohort) and experimental/laboratory studies relating ASD to immune–inflammatory markers or mechanisms. Exclusion: reviews, meta-analyses, editorials, case reports, and duplicates. Risk of bias was rated with RoB 2 (experimental) and JBI tools (observational).Results: Of 3,600 records, 12 studies were included. Across human samples and models, increased monocyte IL-6 production and pro-inflammatory transcriptional signatures were observed, alongside microglial polarization and oxidative stress, suggesting a peripheral–CNS inflammatory circuit. Cohort studies associated maternal immune conditions, infections during pregnancy/early life, and prenatal fever with increased ASD risk. Molecular findings indicated microexon mis-splicing in CPEB4 with synaptic impact. Overall quality ranged from moderate to good; limitations included methodological heterogeneity, small samples, and incomplete control of confounders. Conclusion: The evidence supports contributions of immune–inflammatory mechanisms and maternal exposures to ASD risk and phenotypic expression, underscoring the need for standardized biomarkers and multicenter cohorts for clinical validation.