Thioredoxin level and inflammatory markers in children with autism spectrum disorders

Abd-Allah, Naglaa A.; Ibrahim, Ola M.; Elmalt, Heba A.; Shehata, Manal A.; Hamed, Rania A.; El-Saadouni, Nisrin M; Hawary, Bahaa

doi:10.1186/s43045-020-00021-4

Cited by 6 publications

(10 citation statements)

References 47 publications

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“…All studies included were ageand sex-matched, i.e., there were no significant differences between individuals with ASD and TD controls with respect to age and sex. ASD was diagnosed according to DSM-IV/ICD-10 criteria in fifteen publications [22][23][24][25][26][27][28][29][30]32,[36][37][38][39]43], and to DSM-5, in nine publications [31,[33][34][35]40,41,[44][45][46]. Two register-based studies were included [38,39].…”

Section: General Characteristics Of Eligible Studiesmentioning

confidence: 99%

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

Lugo‐Marín

Gisbert

et al. 2022

IJMS

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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 < 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 = −0.42, 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.

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Section: General Characteristics Of Eligible Studiesmentioning

confidence: 99%

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

Lugo‐Marín

Gisbert

et al. 2022

IJMS

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“…TNF-α, BAFF, IL-4, and IL-5 have been found at increased levels in the sera of patients with ASD compared to healthy controls, and these changes are associated with ASD severity 3 , 20 , 22 , 30 – 32 (Supplemental Table 1 ). Additionally, elevated concentrations of IL-4 and IL-5 were observed in the sera of women at 15–19 weeks of gestation who later gave birth to a child diagnosed with ASD compared to women who gave birth to normal children 33 (Supplemental Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…Our findings suggest that a set of four cytokines (TNF-α, BAFF, IL-4, and IL-5) and a set of ten cytokines (IFN-γ, GM-CSF, TNF-α, IL-2, IL-4, IL-6, IL-17A, BAFF, IL-12p70, and IL-10) could serve as potential biomarkers for ASD and CP, respectively. Additionally, numerous efforts have been directed towards identifying blood-based biomarkers for ASD due to its greater accessibility compared to CSF 3 , 20 , 22 , 30 – 32 , 42 . The consistency of TNF-α, BAFF, IL-4, and IL-5 in the CSF of patients with ASD and TNF-α, IL-6, and IL-10 in the CSF of patients with CP in our study, with previous reports on their presence in the serum of ASD and CP patients 3 , 20 , 22 , 30 – 32 , 42 , suggests the feasibility of determining these cytokines from the blood of patients with ASD and CP for early diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, numerous efforts have been directed towards identifying blood-based biomarkers for ASD due to its greater accessibility compared to CSF 3 , 20 , 22 , 30 – 32 , 42 . The consistency of TNF-α, BAFF, IL-4, and IL-5 in the CSF of patients with ASD and TNF-α, IL-6, and IL-10 in the CSF of patients with CP in our study, with previous reports on their presence in the serum of ASD and CP patients 3 , 20 , 22 , 30 – 32 , 42 , suggests the feasibility of determining these cytokines from the blood of patients with ASD and CP for early diagnosis. This could help avoid unnecessary lumbar punctures, particularly in small children, given the invasive nature of the procedure.…”

Section: Discussionmentioning

confidence: 99%

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Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy

Than,

Nguyen,

Nguyen

et al. 2023

Sci Rep

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Inflammation conditions are associated with autism spectrum disorder (ASD) and cerebral palsy (CP), primarily observed in the peripheral immune system. However, the extent of neuro-inflammation and neuro-immune dysregulation remains poorly studied. In this study, we analyzed the composition of cerebrospinal fluid (CSF) to uncover the inflammatory mediators driving the neuro-immune system in ASD and CP patients. Our findings revealed that ASD patients had elevated levels of four inflammatory cytokines (TNF-α, IL-4, IL-21, and BAFF) compared to controls, while CP patients exhibited increased levels of eight inflammatory cytokines (IFN-γ, GM-CSF, TNF-α, IL-2, IL-4, IL-6, IL-17A and IL-12), one anti-inflammatory cytokine (IL-10), and five growth factors (GFs) (NGF-β, EGF, GDF-15, G-CSF and BMP-9) compared to both controls and ASD patients. Additionally, intrathecal infusion of autologous bone marrow mononuclear cells (BMMNCs) led to a slight decrease in TGF-β and GDF-15 levels in the CSF of ASD and CP patients, respectively. Our study provides new insights into the molecular composition of CSF in ASD and CP patients, with the potential to develop more effective diagnosis methods and improved treatment for these diseases.Clinical trial registration CSF samples used in this study are from clinical trials NCT03225651, NCT05307536, NCT02569775, NCT03123562, NCT02574923, NCT05472428 and previous reports [7, 9, 17–19].

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“…The most widely accepted hypothesis that may explain the rapid increase in ASD prevalence is the combination between genetic susceptibility and environmental factors [4]. While numerous studies have been conducted to investigate the effect of genetic, environmental, and immunological aspects on the etiology of ASD, there is still much to be done to realize the exact etiology [5], [6], [7].…”

Section: Introductionmentioning

confidence: 99%

Comparing Levels of Urinary Phthalate Metabolites in Egyptian Children with Autism Spectrum Disorders and Healthy Control Children: Referring to Sources of Phthalate Exposure

Shehata

Salah

Youssef

et al. 2021

Open Access Maced J Med Sci

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Background: Evidence supporting environmental risk factors of autism spectrum disorder (ASD) is rising. Phthalates are assumed to contribute to this risk due to their extensive use in daily life as plasticizers and additives in numerous customer products. Phthalates are also accused as a neurotoxic agent affecting brain development. Aim: The main objective of this study is to compare the concentrations of urinary phthalate metabolites as biomarkers of phthalate exposure in children with autism to that of a healthy control group and to compare their exposure to suspected environmental sources of phthalate. Methods: It was a case-control study; conducted over a period of one year. Thirty-eight children with ASD and 99 apparently healthy children comprised the control group, were enrolled in the study. Urinary concentrations of four phthalate metabolites were measured, using a combination of solid phase extraction, high pressure liquid chromatography, and tandem mass spectrometry. Results: Children with ASD comprised 38 children (32 boys and 6 girls), their mean age was 8.95 + 4.17 years. There were significant higher levels of urinary Mono (2ethylhexyl) phthalate (MEHP), mono benzyl, and mono butyl phthalates in cases vs. controls with p value equals (0.006, 0.017 and <0.001) respectively. Regression analysis revealed that male gender and the level of mono butyl are the main predictors of ASD (p<0.001). Conclusion: This study suggested a link between phthalates and ASD with higher urinary levels of phthalate metabolites in children with ASD. These high levels are either due to increased exposure or defective metabolism in children with ASD. The study declined any relationship of the studied sources of phthalate exposure to ASD except the exposure to wall painting with plastic.

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Thioredoxin level and inflammatory markers in children with autism spectrum disorders

Cited by 6 publications

References 47 publications

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

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

Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy

Comparing Levels of Urinary Phthalate Metabolites in Egyptian Children with Autism Spectrum Disorders and Healthy Control Children: Referring to Sources of Phthalate Exposure

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