{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:14Z","timestamp":1787028494080,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade inflammation may be involved in the pathophysiology of this condition. However, studies investigating peripheral blood levels of immune cells, and\/or of immune cell activation markers such as neopterin are lacking and have provided mixed findings. We performed a systematic review and meta-analysis of studies comparing total and differential white blood cell (WBC) counts, blood levels of lymphocyte subpopulations and of neopterin between individuals with ASD and typically developing (TD) controls (PROSPERO registration number: CRD CRD42019146472). Online searches covered publications from 1 January 1994 until 1 March 2022. Out of 1170 publication records identified, 25 studies were finally included. Random-effects meta-analyses were carried out, and sensitivity analyses were performed to control for potential moderators. Results: Individuals with ASD showed a significantly higher WBC count (k = 10, g = 0.29, p = 0.001, I2 = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I2 = 31%), monocytes (k = 11, g = 0.35, p &lt; 0.001, I2 = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I2 = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I2 = 82%), and a significantly lower Th\/Tc cells ratio (k = 3, g = \u22120.42, p = 0.008, I2 = 0%), compared to TD controls. Subjects with ASD were also characterized by a significantly higher neutrophil-to-lymphocyte ratio (NLR) (k = 4, g = 0.69, p = 0.040, I2 = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I2 = 97%) compared to TD controls. No significant differences were found with respect to the levels of lymphocytes, B cells, Th cells, Treg cells, and Th17 cells. Sensitivity analysis suggested that the findings for monocyte and neutrophil levels were robust, and independent of other factors, such as medication status, diagnostic criteria applied, and\/or the difference in age or sex between subjects with ASD and TD controls. Taken together, our findings suggest the existence of a chronically (and systemically) activated inflammatory response system in, at least, a subgroup of individuals with ASD. This might have not only diagnostic, but also, therapeutic implications. However, larger longitudinal studies including more homogeneous samples and laboratory assessment methods and recording potential confounding factors such as body mass index, or the presence of comorbid psychiatric and\/or medical conditions are urgently needed to confirm the findings.<\/jats:p>","DOI":"10.3390\/ijms232214329","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T02:52:21Z","timestamp":1668999141000},"page":"14329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Activation of the Monocyte\/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"23","author":[{"given":"Gara","family":"Arteaga-Henr\u00edquez","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Catalonia, Spain"},{"name":"Biomedical Network Research Centre on Mental Health (CIBERSAM), 28029 Madrid, Madrid, Spain"},{"name":"Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d\u2019Hebron Insitute (VHIR), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Lugo-Mar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Catalonia, Spain"},{"name":"Biomedical Network Research Centre on Mental Health (CIBERSAM), 28029 Madrid, Madrid, Spain"},{"name":"Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d\u2019Hebron Insitute (VHIR), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8329-1717","authenticated-orcid":false,"given":"Laura","family":"Gisbert","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Catalonia, Spain"},{"name":"Biomedical Network Research Centre on Mental Health (CIBERSAM), 28029 Madrid, Madrid, Spain"},{"name":"Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d\u2019Hebron Insitute (VHIR), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Catalonia, Spain"},{"name":"Department of Psychiatry and Legal Medicine, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imanol","family":"Seti\u00e9n-Ramos","sequence":"additional","affiliation":[{"name":"Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d\u2019Hebron Insitute (VHIR), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7340-2161","authenticated-orcid":false,"given":"M\u00f3nica","family":"Mart\u00ednez-Gallo","sequence":"additional","affiliation":[{"name":"Department of Immunolgy, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Catalonia, Spain"},{"name":"Diagnostic Immunology Research Group, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Catalonia, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Pujol-Borrell","sequence":"additional","affiliation":[{"name":"Department of Immunolgy, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Catalonia, Spain"},{"name":"Diagnostic Immunology Research Group, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Catalonia, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep Antoni","family":"Ramos-Quiroga","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Hospital Universitari Vall d\u2019Hebron (HUVH), 08035 Barcelona, Catalonia, Spain"},{"name":"Biomedical Network Research Centre on Mental Health (CIBERSAM), 28029 Madrid, Madrid, Spain"},{"name":"Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d\u2019Hebron Insitute (VHIR), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Catalonia, Spain"},{"name":"Department of Psychiatry and Legal Medicine, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"e2130272","DOI":"10.1001\/jamanetworkopen.2021.30272","article-title":"Risk of Self-harm in children and adults with Autism Spectrum Disorder: A systematic Review and Meta-Analysis","volume":"4","author":"Blanchard","year":"2021","journal-title":"JAMA Netw. 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