- PBMC proteomic profiling identified 39 differentially expressed proteins distinguishing children with ASD from typically developing controls, with molecular heterogeneity across ASD subgroups.
- Functional analyses revealed enrichment of cytoskeletal and chromatin associated pathways, including an actin centred protein interaction network linked to ASD.
- DEPs correlated with behavioural, social, emotional, sensory and cognitive phenotypes and overlapped known ASD genes, supporting peripheral proteomics for biologically informed stratification.
Brain Behav Immun Health. 2026 Jul 30;56:101319. doi: 10.1016/j.bbih.2026.101319. eCollection 2026 Oct.
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.
PMID:42602463 | PMC:PMC13473956 | DOI:10.1016/j.bbih.2026.101319
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