{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:09:34Z","timestamp":1790096974099,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2013immune\u2013brain 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.<\/jats:p>","DOI":"10.3390\/ijms27188407","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune and Autoimmune Mechanisms in Autism Spectrum Disorder: Linking Molecular Pathways to Neuropsychological Trajectories Across the Lifespan"],"prefix":"10.3390","volume":"27","author":[{"given":"Rosa Gemma","family":"Viterbo","sequence":"first","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Precision and Regenerative Medicine, Jonic Area University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba","family":"Tritto","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Precision and Regenerative Medicine, Jonic Area University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7347-3199","authenticated-orcid":false,"given":"Dario","family":"Sardella","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Precision and Regenerative Medicine, Jonic Area University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-1731","authenticated-orcid":false,"given":"Pietro","family":"Iaffaldano","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neurosciences-DiBraiN, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-1679","authenticated-orcid":false,"given":"Andrea","family":"De Giacomo","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Precision and Regenerative Medicine, Jonic Area University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(13)61539-1","article-title":"Autism","volume":"383","author":"Lai","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/S0140-6736(18)31129-2","article-title":"Autism spectrum disorder","volume":"392","author":"Lord","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S1474-4422(15)00044-7","article-title":"Gene hunting in autism spectrum disorder: On the path to precision medicine","volume":"14","author":"Geschwind","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1001\/jama.2017.12141","article-title":"The heritability of autism spectrum disorder","volume":"318","author":"Sandin","year":"2017","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nrn3978","article-title":"Immune mediators in the brain and periphery in autism spectrum disorder","volume":"16","author":"Estes","year":"2015","journal-title":"Nat. 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