Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy

Than, Uyen Thi Trang; Nguyen, Liem Thanh; Nguyen, Phuong Hoang; Nguyen, Xuan-Hung; Trinh, Dong Phuong; Hoang, Diem Huong; Nguyen, Phuong Anh Thi; Dang, Van Duc

doi:10.1038/s41598-023-49902-8

Cited by 15 publications

(3 citation statements)

References 48 publications

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“…However, this study reported no significant correlation between the level of TNF-α in serum and CSF, and the use of small sample sizes may be responsible for non-conclusive tests. Presence of neuroinflammation is further supported by a recent study that found elevated levels of TNF-α and interleukins (Than et al, 2023) in ASD.…”

Section: Methodsmentioning

confidence: 65%

Characteristics of Cerebrospinal Fluid in Autism Spectrum Disorder - A Systematic Review

Srivastava,

O’Reilly

2024

Preprint

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Autism Spectrum Disorder (ASD) is a range of neurodevelopmental conditions characterized by impaired social interaction, learning, and restricted or repetitive behaviors. The underlying causes of ASD are still debated, but researchers have found many physiological traits to help understand the etiology of ASD.Some of the features that characterize people with ASD are immune markers (e.g. increased lymphocytes, cytokine levels), decreased neuropeptides like oxytocin and arginine vasopressin, folate deficiency, change in brain anatomy and physiology, and increased extra axial cerebrospinal fluid (CSF). CSF has a critical role in maintaining the homeostasis of the neuronal environment and has, therefore, been analyzed in multiple conditions that impact the central nervous system. The study of CSF is critical in understanding neurological disorders as its composition changes with the disorders, and these changes may indicate various disorder-related physiological mechanisms. For this systematic review, we searched the PubMed database for studies published between 1977 and 2023. We found 54 studies from 276 eligible for this review after manual screening. We took stock of the evidence supporting the hypothesis that ASD alters the properties and composition of CSF. We systematically report on the different attributes of CSF in the ASD population that could 1) be potential biomarkers, 2) assist in understanding the origins and progression of ASD, and 3) shed light on the aspects of the relationship between ASD and the immune system.

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Section: Methodsmentioning

confidence: 65%

Characteristics of Cerebrospinal Fluid in Autism Spectrum Disorder - A Systematic Review

Srivastava,

O’Reilly

2024

Preprint

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“…Furthermore, our study emphasizes the connection between IL-17 A, a pro-inflammatory cytokine, and the severity of ASD. Dysregulated cytokine levels, indicative of immune system dysfunction and potential neuroinflammation, have been reported in individuals with ASD [ 43 ]. Elevated IL-17 A levels in children with ASD provide additional support for the involvement of inflammatory processes in the pathogenesis of ASD.…”

Section: Discussionmentioning

confidence: 99%

Serum interleukin-17 A and homocysteine levels in children with autism

Li,

Dang,

Yan

2024

BMC Neurosci

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Background Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that typically emerges early in childhood. This study aimed to explore the potential link between serum levels of vitamin B12 and homocysteine (Hcy) and the severity of ASD symptoms in children. Methods In this study, 50 children diagnosed with ASD comprised the observation group, while 50 healthy children constituted the control group. Serum levels of IL-17 A, Hcy, folate, and vitamin B12 were compared between the study group and control group, as well as among children with different degrees of ASD severity. The correlation between the Childhood Autism Rating Scale (CARS) score and serum levels of IL-17 A, Hcy, folate, and vitamin B12 was examined. Additionally, the relationship between serum IL-17 A and Hcy levels and their association with the severity ASD were explored. Results Compared to the control group, the observation group demonstrated elevated serum Hcy and IL-17 A levels alongside decreased folate and vitamin B12 levels. Individuals with severe ASD exhibited higher Hcy and IL-17 A levels but lower folate and vitamin B12 levels compared to those with mild to moderate ASD. The CARS score showed negative correlations with serum folate and vitamin B12 levels and positive correlations with serum IL-17 A and Hcy levels in ASD patients. Additionally, serum Hcy and IL-17 A levels were correlated with ASD severity. Conclusion Children diagnosed with ASD presented with reduced serum vitamin B12 levels and increased levels of Hcy, potentially contributing to the onset and severity of ASD.

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“…Brain-based abnormalities include abnormalities in monoamine neurotransmitter production, imbalances in the excitatory to inhibitory balance, and epilepsy [3][4][5]. Systemic abnormalities including immune dysfunction, oxidative stress and metabolic disorders may also be linked with ASD [6][7][8][9][10]. These abnormalities can interact to negatively reinforce each other.…”

Section: Introductionmentioning

confidence: 99%

Binding Folate Receptor Alpha Autoantibody Is a Biomarker for Leucovorin Treatment Response in Autism Spectrum Disorder

Frye,

McCarty,

Werner

et al. 2024

JPM

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Autism spectrum disorder (ASD) affects up to 1 in 36 children in the United States. It is a heterogeneous neurodevelopmental disorder with life-long consequences. Patients with ASD and folate pathway abnormalities have demonstrated improved symptoms after treatment with leucovorin (folinic acid), a reduced form of folate. However, biomarkers for treatment response have not been well investigated and clinical trials are lacking. In this retrospective analysis, a cohort of prospectively collected data from 110 consecutive ASD clinic patients [mean (SD) age: 10.5 (6.2) years; 74% male] was examined. These patients all underwent testing for folate receptor alpha autoantibodies (FRAAs) and soluble folate binding proteins (sFBPs) biomarker and were treated with leucovorin, if appropriate. Analyses examined whether these biomarkers could predict response to leucovorin treatment as well as the severity of ASD characteristics at baseline. The social responsiveness scale (SRS), a measure of core ASD symptoms, and the aberrant behavior checklist (ABC), a measure of disruptive behavior, were collected at each clinic visit. Those positive for sFBPs had more severe ASD symptoms, and higher binding FRAA titers were associated with greater ABC irritability. Treatment with leucovorin improved most SRS subscales with higher binding FRAA titers associated with greater response. Leucovorin treatment also improved ABC irritability. These results confirm and expand on previous studies, underscore the need for biomarkers to guide treatment of folate pathways in ASD, and suggest that leucovorin may be effective for children with ASD.

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Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy

Cited by 15 publications

References 48 publications

Characteristics of Cerebrospinal Fluid in Autism Spectrum Disorder - A Systematic Review

Characteristics of Cerebrospinal Fluid in Autism Spectrum Disorder - A Systematic Review

Serum interleukin-17 A and homocysteine levels in children with autism

Binding Folate Receptor Alpha Autoantibody Is a Biomarker for Leucovorin Treatment Response in Autism Spectrum Disorder

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