ArticleBrain, behavior, & immunity - health2026
Peripheral blood mononuclear cell proteomic profiling reveals cytoskeletal- and chromatin-associated protein signatures in autism spectrum disorder.
Article in Brain, behavior, & immunity - health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: We aimed to identify protein patterns in peripheral blood mononuclear cells (PBMCs) associated with autism spectrum disorder (ASD) diagnosis and clinical heterogeneity and to explore their relevance to biological processes implicated in ASD. Methods: PBMC proteomic profiles were examined in a Thai cross-sectional cohort of 191 children with ASD and 106 typically developing (TD) controls. Mass spectrometry (LC-MS/MS) was performed to identify differentially expressed proteins (DEPs). Exploratory classification performance was assessed by ROC analysis across clinical subgroups. Associations between DEPs and behavioral and cognitive symptoms were evaluated using mixOmics multivariate integration. DEPs were further assessed for overlap with ASD-associated genes and previously reported ASD blood and brain proteomic datasets, and functionally annotated using protein-protein interaction and enrichment analyses. Results: Thirty-nine annotated proteins were differentially expressed between children with ASD and TD controls, while a subset was associated with heterogeneity within ASD. Several DEPs were encoded by known ASD-associated genes and overlapped with proteins previously reported in ASD blood and brain studies. Functional analyses identified enrichment of cytoskeletal and chromatin-associated pathways, including an actin-centered protein interaction network. Multivariate integration analyses revealed associations between these proteins and behavioral, social, emotional, sensory, and cognitive phenotypes, while subgroup analyses indicated subtle molecular heterogeneity within ASD. Conclusion: PBMC proteomic profiles identified molecular signatures associated with ASD diagnosis and clinical heterogeneity in this discovery cohort. Exploratory network analyses highlighted cytoskeletal- and chromatin-associated proteins, supporting further evaluation of peripheral proteomics as a tool for investigating ASD biology and biologically informed stratification.
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