Cerebrospinal Fluid and Serum Markers of Inflammation in Autism

Zimmerman, Andrew W.; Jyonouchi, Harumi; Comi, Anne M.; Connors, Susan L.; Milstien, Sheldon; Varsou, Angeliki; Heyes, Melvyn P.

doi:10.1016/j.pediatrneurol.2005.03.014

Cited by 271 publications

(165 citation statements)

References 32 publications

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“…28,34 The current proteomic study has identified a number of circulating proteins that appear to be abnormal in autism compared with controls. Five peptide components showed the biggest differences between the Autism and the Typical groups, four of which correspond to three proteins involved in the complement pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the changes reported in cytokine levels may occur in separate subgroups of autism subjects that have different clinical phenotypes. [28][29][30][31][32][33][34] Other immune system alterations reported in subjects who have autism include the presence of autoantibodies in the blood directed to central nervous system (CNS) or brain antigens, and the presence of inflammation within the brain. [35][36][37][38] Finally, an increased frequency of autoimmune disorders has been described in the families of individuals with autism.…”

Section: Introductionmentioning

confidence: 99%

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A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Corbett

Kantor²,

Schulman³

et al. 2006

Mol Psychiatry

167

113

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Modern methods that use systematic, quantitative and unbiased approaches are making it possible to discover proteins altered by a disease. To identify proteins that might be differentially expressed in autism, serum proteins from blood were subjected to trypsin digestion followed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF) instruments to identify differentially expressed peptides. Children with autism 4-6 years of age (n = 69) were compared to typically developing children (n = 35) with similar age and gender distributions. A total of 6348 peptide components were quantified. Of these, five peptide components corresponding to four known proteins had an effect size > 0.99 with a P < 0.05 and a Mascot identification score of 30 or greater for autism compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism. Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain. Despite limitations of the study, including the low fold changes and variable detection rates for the peptide components, the data support possible differences of circulating proteins in autism, and should help stimulate the continued search for causes and treatments of autism by examining peripheral blood.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Corbett

Kantor²,

Schulman³

et al. 2006

Mol Psychiatry

167

113

View full text Add to dashboard Cite

show abstract

“…Hamberger et al [89] described four patients with Rett´s syndrome who had significantly elevated CSF glutamate levels, thought to originate from microglia. There is also compelling evidence that chronic activation of microglia results in a predominant neurotoxic effect on the brain, with excitotoxic levels of glutamate being secreted [90,91]. This means that chronic activation of microglia creates an environment hostile to developing neurons, dendrites and synapses.…”

Section: The Role Of Microgliamentioning

confidence: 99%

Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders

Blaylock

Strunecká

2009

CMC

125

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Despite the great number of observations being made concerning cellular and the molecular dysfunctions associated with autism spectrum disorders (ASD), the basic central mechanism of these disorders has not been proposed in the major scientific literature. Our review brings evidence that most heterogeneous symptoms of ASD have a common set of events closely connected with dysregulation of glutamatergic neurotransmission in the brain with enhancement of excitatory receptor function by pro-inflammatory immune cytokines as the underlying mechanism. We suggest that environmental and dietary excitotoxins, mercury, fluoride, and aluminum can exacerbate the pathological and clinical problems by worsening excitotoxicity and by microglial priming. In addition, each has effects on cell signaling that can affect neurodevelopment and neuronal function. Our hypothesis opens the door to a number of new treatment modes, including the nutritional factors that naturally reduce excitotoxicity and brain inflammation.

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“…Children with ASD have been noted to have increased levels of the pro-inflammatory cytokines MCP-1, interleukin (IL)-6, interferon-␣, INF-␥ and tumor necrosis factor-␣ (TNF-␣) in the brain or in the circulating blood. [15][16][17][18][19] Inflammation may mediate specific symptoms in ASD. For example, children with ASD and gastrointestinal symptoms were noted to have increased T-lymphocyte production of the pro-inflammatory cytokines, TNF-␣, and INF-␥ but decreased T-lymphocyte production of the anti-inflammatory cytokine, IL-10 in colonic, upper and lower small intestinal tissue.…”

Section: Inflammationmentioning

confidence: 99%

Improving the Prediction of Response to Therapy in Autism

Bent

Hendren

2010

Neurotherapeutics

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Summary: Autism is a heterogeneous disorder involving complex mechanisms and systems occurring at diverse times. Because an individual child with autism may have only a subset of all possible abnormalities at a specific time, it may be challenging to identify beneficial effects of an intervention in double-blind, randomized, controlled trials, which compare the mean responses to treatments. Beneficial effects in a small subset of children may be obscured by the lack of effect in the majority. We review the evidence for several potential model systems of biochemical abnormalities that may contribute to the etiology of autism, we describe potential biomarkers or treatment targets for each of these abnormalities, and we provide illustrative treatment trials using this methodology. Potential model systems include immune over and under reactivity, inflammation, oxidative stress, free fatty acid metabolism, mitochondrial dysfunction, and excitotoxicity. Including potential biomarkers and targeted treatments in clinical trials for autism provides a potential method for limiting the heterogeneity of enrolled subjects, which may improve the power of studies to identify beneficial effects of treatments while also improving the understanding of the disease.

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Cerebrospinal Fluid and Serum Markers of Inflammation in Autism

Cited by 271 publications

References 32 publications

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders

Improving the Prediction of Response to Therapy in Autism

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