Plasma Cytokine Profiles in Subjects with High-Functioning Autism Spectrum Disorders

Suzuki, Katsuaki; Matsuzaki, Hideo; Iwata, Koichi; Kameno, Yosuke; Shimmura, Chie; Kawai, Shinya; Yoshihara, Yujiro; Wakuda, Tomoyasu; Takebayashi, Kiyokazu; Takagai, Shu; Matsumoto, Kaori; Tsuchiya, Kenji J.; Iwata, Yasuhide; Nakamura, Kazuhiko; Tsujii, Masatsugu; Sugiyama, Tomoya; Mori, Norio

doi:10.1371/journal.pone.0020470

Cited by 224 publications

(178 citation statements)

References 36 publications

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“…Th17 cells and their cytokine mediators have been suggested to have a role in ASD. Increased levels of IL-17 have been found in blood from subjects with ASD [19,39,40]. In the maternal immune activation (MIA) mouse model of ASD, systemic blockage of IL-17 inhibited the MIA-induced ASD-like behavior in the offspring, suggesting that IL-17 plays an important role during the pathophysiological process of ASD [41].…”

Section: Discussionmentioning

confidence: 99%

Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents

Fagan¹,

Crider²,

Ahmed³

et al. 2017

Complex Psychiatry

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder with hallmark symptoms including social deficits, communication deficits and repetitive behaviors. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of ASD. The complement system represents one of the major effector mechanisms of the innate immune system, and regulates inflammation, and orchestrates defense against pathogens. However, the role of CNS complement system in ASD is not well understood. In the present study, we found a significant increase in C2, C5, and MASP1, but a decrease in C1q, C3, and C4 mRNA levels in the middle frontal gyrus of ASD subjects compared to controls. Significant decreases in the mRNA levels of 2 key proinflammatory cytokines, IL-17 and IL-23 were observed in ASD subjects. Our study further demonstrated a strong association of complement genes with IL-17 and IL-23, suggesting a possible role of the complement system in immune dysregulation in ASD. We observed significant associations between complement components and abnormality of development scores in subjects with ASD. In rodents, C3 knockdown in the prefrontal cortex induced social interaction deficits and repetitive behavior in mice. Together, these studies suggest a potential role of C3 in the pathophysiology of ASD.

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Section: Discussionmentioning

confidence: 99%

Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents

Fagan¹,

Crider²,

Ahmed³

et al. 2017

Complex Psychiatry

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“…5,6 Earlier studies have documented prominent microglial activation and increased production of inflammatory cytokines and chemokines, including interferon gamma (IFN-g), interleukin (IL)-1b, IL-6, IL-12p40, tumor necrosis factor alpha (TNF-a), and chemokine (C-C motif) ligand 2 (CCL2) in the brain tissue and cerebrospinal fluid (CSF) of some individuals with ASD. 3,7 Although findings are not consistent, there is growing evidence indicating elevated plasma levels of pro-inflammatory cytokines, including TNF-a, IFN-g, IL-1b, IL-6, IL-12, IL-17A, IL-23, [8][9][10][11][12][13][14][15] and decreased plasma levels of the anti-inflammatory cytokines IL-10 and transforming growth factor-beta (TGF-b) in children with ASD as compared to controls. 1,16 Although the phenotypic and neurobiological heterogeneity in ASD might be underlying factors that account for inconsistent findings, it should also be noted that important confounding factors influencing immune markers, such as medication and body mass index (BMI), have not been adequately addressed in previous research.…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

Gülöksüz

Abali

Çetin

et al. 2017

Rev. Bras. Psiquiatr.

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Objective: To investigate plasma concentrations of S100B (a calcium-binding protein derived primarily from the glia) and inflammatory cytokines in children with autism and the relationship between S100B and cytokine concentrations. Methods: Plasma levels of S100B, tumor necrosis factor alpha (TNF-a), interferon gamma, interleukin (IL)-1b, IL-4, IL-6, IL-10, and IL-17A were measured in 40 unmedicated children with autism and 35 normally developing healthy children. The severity of autism was assessed using the Childhood Autism Rating Scale (CARS). Results: Concentrations of both S100B and TNF-a were higher in children with autism before and after adjusting for a priori-selected confounders (age, sex, and body mass index). S100B concentrations were higher in children with severe autism compared to children with mild-moderate autism. However, this association remained as a trend after adjusting for confounders. S100B concentrations correlated positively with TNF-a concentrations. Conclusion: Our findings showing an increase in peripheral concentrations of S100B and TNF-a provide limited support to the hypothesis about the roles of altered immune function and S100B in autism spectrum disorder (ASD). Studies of larger numbers of well-characterized individuals with ASD are needed to clarify the potential role of the immune system in the pathophysiology of this disorder.

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“…Another cytokine that seems to be implicated in ASD is TGF-β 1 , which is decreased in plasma levels of children with autism when compared with typically developing controls [6]. Interestingly, a recent study investigating several immune mediators found an increase of IL-17 in autistic patients, suggesting that Th17 response may be also involved in ASD [7]. Even though all these papers have shown changes in immune parameters in ASD, it is not clear whether the immune system is involved in the onset of ASD.…”

Section: Introductionmentioning

confidence: 99%

Changes in Adipokine Levels in Autism Spectrum Disorders

et al. 2013

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Background and Objective: The etiopathogenesis of autism spectrum disorders (ASD) is largely unknown, but it seems to involve dysfunction in several biological systems. Among many possible biological pathways, the immune system has emerged as potentially involved. Recent studies have shown association between cytokines (molecules that mediate immune cell interaction) and ASD. Adipokines are cytokines secreted mainly by adipose tissue and may have systemic effects. The main objective of this study was to compare the plasma levels of three adipokines between patients with ASD and healthy controls. Another aim was to correlate the levels of these adipokines and the severity of autistic symptoms as measured by the Social Responsiveness Scale (SRS). Methods: We collected plasma from 30 patients and 19 controls and measured the levels of adiponectin, leptin and resistin using a commercially available kit. We also used the SRS as a tool to assess the severity of autistic symptoms. Results: We found decreased levels of resistin, increased levels of leptin and unaltered levels of adiponectin in plasma from ASD subjects in comparison with controls. There was also a negative correlation between the levels of adiponectin and the severity of symptoms as assessed by the SRS. Conclusion: There are significant changes in the plasma levels of adipokines from patients with ASDs. They suggest the occurrence of systemic changes in ASD and may be hallmarks of the disease.

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Plasma Cytokine Profiles in Subjects with High-Functioning Autism Spectrum Disorders

Cited by 224 publications

References 36 publications

Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents

Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents

Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

Changes in Adipokine Levels in Autism Spectrum Disorders

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