Alterations in plasma cytokine levels in chinese children with autism spectrum disorder

Hu, Chun-Chun; Xu, Xiu; Xiong, Guoliang; Xu, Qiong; Zhou, Bo; Li, Chunyang; Qi, Qin; Liu, Chunxue; Li, Huiping; Sun, Yunjun; Yu, Xiang

doi:10.1002/aur.1940

Cited by 48 publications

(30 citation statements)

References 48 publications

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“…Plasma cytokine levels have been shown to be altered in 87 Chinese ASD children (2–6 years old). In this study, eotaxin, TGF-b and TNF-α were up-regulated while no differences were observed in IL-8 levels between ASD (assessed using the Autism Diagnostic Observation Schedule, second edition, ADOS-2) and 41 normally developing age-matched control children [ 19 ]. Interestingly, in this study, most of the recruited ASD children were between the moderate and severe end of the ADOS-2 scale.…”

Section: Inflammatory Conditions In Autism Spectrum Disordersmentioning

confidence: 99%

Inflammation and Neuro-Immune Dysregulations in Autism Spectrum Disorders

Siniscalco

Schultz

Brigida³

et al. 2018

Pharmaceuticals

208

113

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Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and interaction and restricted-repetitive patterns of behavior, interests, or activities. Strong inflammation states are associated with ASD. This inflammatory condition is often linked to immune system dysfunction. Several cell types are enrolled to trigger and sustain these processes. Neuro-inflammation and neuro-immune abnormalities have now been established in ASD as key factors in its development and maintenance. In this review, we will explore inflammatory conditions, dysfunctions in neuro-immune cross-talk, and immune system treatments in ASD management.

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Section: Inflammatory Conditions In Autism Spectrum Disordersmentioning

confidence: 99%

Inflammation and Neuro-Immune Dysregulations in Autism Spectrum Disorders

Siniscalco

Schultz

Brigida³

et al. 2018

Pharmaceuticals

208

113

View full text Add to dashboard Cite

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“…Several lines of evidence point to ongoing and prominent activation of innate myeloid immune cells in ASD (Ashwood et al, 2011;Enstrom et al, 2010;Hu et al, 2018;Inga Jácome et al, 2016;Molloy et al, 2006). Furthermore, we and others have shown increased activation of circulating myeloid cells in the periphery following ex vivo stimulation, including changes in gene expression and the release of pro-inflammatory cytokines (Ashwood et al, 2011;Enstrom et al, 2010;Mendizabal et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Genetic variants drive altered epigenetic regulation of endotoxin tolerance in BTBR macrophages

Ciernia

Link

Careaga³

et al. 2020

Preprint

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The BTBR T + Itpr3 tf /J (BTBR) mouse has been used as a complex genetic model of Autism Spectrum Disorders (ASD). While the specific mechanisms underlying BTBR behavioral phenotypes are poorly understood, prior studies have implicated profound differences in innate immune system control of pro-inflammatory cytokines. Innate immune activation and elevated pro-inflammatory cytokines are also detected in blood of children with ASD. In this study, we examined how underlying BTBR genetic variants correspond to strain-specific changes in chromatin accessibility, resulting in a proinflammatory response specifically in BTBR bone marrow derived macrophages (BMDM). In response to repeated lipopolysaccharide (LPS) treatments, C57BL/6J (C57) BMDM exhibited intact endotoxin tolerance. In contrast, BTBR BMDM exhibited hyper-responsive expression of genes that were normally tolerized in C57. This failure in formation of endotoxin tolerance in BTBR was mirrored at the level of chromatin accessibility. Using ATAC-seq, we specifically identified promoter and enhancer regions with strain-specific differential chromatin accessibility both at baseline and in response to LPS. Regions with strain-specific differences in chromatin accessibility were significantly enriched for BTBR genetic variants, such that an average of 22% of the differential chromatin regions had at least one variant. Together, these results demonstrate that BTBR genetic variants contribute to altered chromatin responsiveness to endotoxin challenge and a failure in formation of tolerance, resulting in a hyperresponsive innate immunity in BTBR. These findings provide evidence for an interaction between complex genetic variants and differential epigenetic regulation of innate immune responses. Our findings also provide novel mechanistic insight into the complex genetic architecture and immune abnormalities observed in ASD.

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“…Multiple studies have demonstrated that TNFα levels are increased in serum of individuals with ASD when compared to controls ( 21 , 23 , 25 , 26 , 34 – 36 ); however, studies on plasma have provided conflicting results ( 4 , 28 , 35 ). These discordant results may reflect the matrix used as well as methodological issues, including different assessment instruments, and clinical and demographic characteristics of ASD populations studied.…”

Section: Discussionmentioning

confidence: 99%

Differential T Cell Levels of Tumor Necrosis Factor Receptor-II in Children With Autism

Ashwood

2018

Front. Psychiatry

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Autism spectrum disorders (ASD) are characterized by impairments in verbal and non-verbal communication, in social interactions, and often accompanied by stereotypical interests and behaviors. A role for immune dysfunction has long been implicated in ASD pathophysiology, behavioral severity, and co-morbidities. The pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) has been associated with ASD in some studies but little is known about its receptors. There are two receptors for TNFα, with TNFRI relaying many of the signals from TNFα, especially those that are rapid, whilst TNFRII relays later more long-term effects of TNFα. Proteolytic cleavage can lead to the soluble versions of these receptors which can neutralize the effects of TNFα. Here, we determined levels of TNFα and its receptors in 36 children with a confirmed diagnosis of ASD and 27 confirmed typically developing (TD) controls, 2–5 years-of-age. Children with ASD had higher levels of TNFRII on T cells compared to controls following cell stimulation. Levels of sTNFRII were decreased in cell supernatants following stimulation in ASD. Overall these data corroborate the role of inflammatory events in ASD and align with previous studies that have shown differential changes in cellular adaptive immunity in children with ASD. Future longitudinal analyzes of cellular immune function and downstream signaling from immune receptors will help further delineate the role of inflammation in ASD.

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Alterations in plasma cytokine levels in chinese children with autism spectrum disorder

Cited by 48 publications

References 48 publications

Inflammation and Neuro-Immune Dysregulations in Autism Spectrum Disorders

Inflammation and Neuro-Immune Dysregulations in Autism Spectrum Disorders

Genetic variants drive altered epigenetic regulation of endotoxin tolerance in BTBR macrophages

Differential T Cell Levels of Tumor Necrosis Factor Receptor-II in Children With Autism

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