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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

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 cel...

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Autores principales: Arteaga-Henríquez, Gara, Lugo-Marín, Jorge, Gisbert, Laura, Setién-Ramos, Imanol, Martínez-Gallo, Mónica, Pujol-Borrell, Ricardo, Ramos-Quiroga, Josep Antoni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699353/
https://www.ncbi.nlm.nih.gov/pubmed/36430805
http://dx.doi.org/10.3390/ijms232214329
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author Arteaga-Henríquez, Gara
Lugo-Marín, Jorge
Gisbert, Laura
Setién-Ramos, Imanol
Martínez-Gallo, Mónica
Pujol-Borrell, Ricardo
Ramos-Quiroga, Josep Antoni
author_facet Arteaga-Henríquez, Gara
Lugo-Marín, Jorge
Gisbert, Laura
Setién-Ramos, Imanol
Martínez-Gallo, Mónica
Pujol-Borrell, Ricardo
Ramos-Quiroga, Josep Antoni
author_sort Arteaga-Henríquez, Gara
collection PubMed
description 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, I(2) = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I(2) = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I(2) = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I(2) = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I(2) = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I(2) = 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, I(2) = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I(2) = 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.
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spelling pubmed-96993532022-11-26 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 Arteaga-Henríquez, Gara Lugo-Marín, Jorge Gisbert, Laura Setién-Ramos, Imanol Martínez-Gallo, Mónica Pujol-Borrell, Ricardo Ramos-Quiroga, Josep Antoni Int J Mol Sci Review 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, I(2) = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I(2) = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I(2) = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I(2) = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I(2) = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I(2) = 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, I(2) = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I(2) = 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. MDPI 2022-11-18 /pmc/articles/PMC9699353/ /pubmed/36430805 http://dx.doi.org/10.3390/ijms232214329 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Arteaga-Henríquez, Gara
Lugo-Marín, Jorge
Gisbert, Laura
Setién-Ramos, Imanol
Martínez-Gallo, Mónica
Pujol-Borrell, Ricardo
Ramos-Quiroga, Josep Antoni
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699353/
https://www.ncbi.nlm.nih.gov/pubmed/36430805
http://dx.doi.org/10.3390/ijms232214329
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