20 Papers / ASD Subtypes / Autism Biomarkers / Autoimmunity / Cytokines / GI / Immune / Inflammation / Males / Parental reports / Review / Seizure

Another Step Toward Defining an Immune-Mediated Subtype of Autism Spectrum Disorder

Excerpts:

“The likelihood of the child having ASD more than doubled among children with food allergy compared with those without food allergy; children with respiratory and skin allergy were also significantly more likely to have ASD, but at a lesser magnitude. While no sex difference was found for food allergy, boys with ASD were significantly more likely than girls with ASD to have respiratory and skin allergy.”

” It may be that GI dysfunction, seizures, and sleep disorder, in addition to food, respiratory, and skin allergies, are medical comorbidities that characterize the immune-mediated subtype of ASD.”

“In the Discussion section of their article, Xu and colleagues review other aspects of immune dysfunction reported in ASD, including abnormalities in peripheral immunoglobulins, imbalance of T-cell subsets, and increased levels of proinflammatory cytokines in postmortem brains of patients with ASD. Considering the significant association between food, respiratory, and skin allergy in children with ASD reported by Xu and colleagues, in conjunction with numerous studies documenting aspects of immune dysfunction in patients with ASD and specific animal models of ASD, evidence continues to mount that an immune-mediated subtype of ASD should continue to be pursued and defined.”

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  • June 8, 2018
Autism Biomarkers / Autoimmunity / Cytokines / GI / Immune / Males / Parental reports / Review / Seizure

Association of Food Allergy and Other Allergic Conditions With Autism Spectrum Disorder in Children

CONCLUSIONS AND RELEVANCE In a nationally representative sample of US children, a significant and positive association of common allergic conditions, in particular food allergy, with ASD was found. Further investigation is warranted to elucidate the causality and underlying mechanism

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  • June 8, 2018
Adenosine / Folate / Glutathione / Homocysteine / Methionine / Methylation / Oxidative Stress / Transsulfuration

Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically-developing peers: A comparison and validation study

Abstract

Autism spectrum disorder (ASD) is a developmental disorder which is currently only diagnosed through behavioral testing. Impaired folate‐dependent one carbon metabolism (FOCM) and transsulfuration (TS) pathways have been implicated in ASD, and recently a study involving multivariate analysis based upon Fisher Discriminant Analysis returned very promising results for predicting an ASD diagnosis. This article takes another step toward the goal of developing a biochemical diagnostic for ASD by comparing five classification algorithms on existing data of FOCM/TS metabolites, and also validating the classification results with new data from an ASD cohort. The comparison results indicate a high sensitivity and specificity for the original data set and up to a 88% correct classification of the ASD cohort at an expected 5% misclassification rate for typically‐developing controls. These results form the foundation for the development of a biochemical test for ASD which promises to aid diagnosis of ASD and provide biochemical understanding of the disease, applicable to at least a subset of the ASD population.

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  • May 14, 2018
Cytokines / First Month / IL-10 / IL-4 / Inflammation / Preterm

The risk of neurodevelopmental disorders at age 10 years associated with blood concentrations of interleukins 4 and 10 during the first postnatal month of children born extremely preterm

Excerpt:
“CONCLUSION: Among children born EP, those who had top quartile concentrations of IL-4 and/or IL-10 on postnatal days 21 and/or 28 were more likely than their peers to have low scores on components of the NEPSY-II, OWLS-II, and WIAT-III assessments, as well as identification as having an ASD.”

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  • May 12, 2018
Adjuvant / Aluminum / Autoimmunity / Genes / GI / Immune

Aluminum Adjuvant-Containing Vaccines in the Context of the Hygiene Hypothesis: A Risk Factor for Eosinophilia and Allergy in a Genetically Susceptible Subpopulation?

Abstract

There are similarities between the immune response following immunization with aluminum adjuvants and the immune response elicited by some helminthic parasites, including stimulation of immunoglobulin E (IgE) and eosinophilia. Immunization with aluminum adjuvants, as with helminth infection, induces a Th2 type cell mediated immune response, including eosinophilia, but does not induce an environment conducive to the induction of regulatory mechanisms. Helminths play a role in what is known as the hygiene hypothesis, which proposes that decreased exposure to microbes during a critical time in early life has resulted in the increased prevalence and morbidity of asthma and atopic disorders over the past few decades, especially in Western countries. In addition, gut and lung microbiome composition and their interaction with the immune system plays an important role in a properly regulated immune system. Disturbances in microbiome composition are a risk factor for asthma and allergies. We propose that immunization with aluminum adjuvants in general is not favorable for induction of regulatory mechanisms and, in the context of the hygiene hypothesis and microbiome theory, can be viewed as an amplifying factor and significant contributing risk factor for allergic diseases, especially in a genetically susceptible subpopulation.

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  • May 3, 2018
Aluminum / Genes / Glial Cells / Inflammation

Aluminium in brain tissue in autism

Abstract
Autism spectrum disorder is a neurodevelopmental disorder of unknown aetiology. It is suggested to involve both genetic susceptibility and environmental factors including in the latter environmental toxins. Human exposure to the environmental toxin aluminium has been linked, if tentatively, to autism spectrum disorder. Herein we have used transversely heated graphite furnace atomic absorption spectrometry to measure, for the first time, the aluminium content of brain tissue from donors with a diagnosis of autism. We have also used an aluminium-selective fluor to identify aluminium in brain tissue using fluorescence microscopy. The aluminium content of brain tissue in autism was consistently high. The mean (standard deviation) aluminium content across all 5 individuals for each lobe were 3.82(5.42), 2.30(2.00), 2.79(4.05) and 3.82(5.17) μg/g dry wt. for the occipital, frontal, temporal and parietal lobes respectively. These are some of the highest values for aluminium in human brain tissue yet recorded and one has to question why, for example, the aluminium content of the occipital lobe of a 15 year old boy would be 8.74 (11.59) μg/g dry wt.? Aluminium-selective fluorescence microscopy was used to identify aluminium in brain tissue in 10 donors. While aluminium was imaged associated with neurones it appeared to be present intracellularly in microglia-like cells and other inflammatory non-neuronal cells in the meninges, vasculature, grey and white matter. The pre-eminence of intracellular aluminium associated with non-neuronal cells was a standout observation in autism brain tissue and may offer clues as to both the origin of the brain aluminium as well as a putative role in autism spectrum disorder.

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  • March 18, 2018
20 Papers / Adjuvant / Aluminum / Apoptosis / COMT / Cytokines / Dendritic cells / Detoxification / Genes / GI / Glial Cells / Glutathione / Immune / Inflammation / Mercury / Methionine / Methylation / Mitochondria / MTHFR / Neuroinflammation / Neurons / Oxidative Stress / Pregnancy / Review / Seizure / Thimerosal / Toxicants / Transsulfuration

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

Excerpt:
“The literature strongly supports that autism is most accurately seen as an acquired cellular detoxification deficiency syndrome with heterogeneous genetic predisposition that manifests pathophysiologic consequences of accumulated, run-away cellular toxicity. At a more general level, it is a form of a toxicant-induced loss of tolerance of toxins, and of chronic and sustained ER overload (“ER hyperstress”), contributing to neuronal and glial apoptosis via the unfolded protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal re-toxification in neurons and glial cells accompanied by chronic UPR is key.”

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  • March 16, 2018
Mercury / Thimerosal / Toxicants / Vaccine Schedule

Protective role of alpha-lipoic acid in impairments of social and stereotyped behaviors induced by early postnatal administration of thimerosal in male rat.

“CONCLUSIONS:
the results of this preclinical study, consistent with previous studies on mice and rats, reveals that neonatal dose-dependent exposure to Thimerosal mimicking the childhood vaccine schedule can induce abnormal social interactions and stereotyped behaviors similar to those observed in neurodevelopmental disorders such as autism, and, for the first time, revealed that these abnormalities may be ameliorated by ALA. This indicates that ALA may protect against mercurial-induced abnormal behaviors.”

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  • February 24, 2018
Cytokines / GI / Inflammation

Biological plausibility of the gut-brain axis in autism

Abstract
Organic abnormalities with neuroinflammatory and psychiatric consequences involving abnormal kynurenine and purine metabolism, neurotransmitter and cytokine imbalances, and altered levels of nutrients and metabolites are noted in autism, and many of these abnormalities-specifically including increased intestinal permeability, microbial metabolites, and heightened serum levels of endotoxin-originate from the gut.

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  • November 1, 2017

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