Immune

The immune system distinguishes self from nonself and eliminates potentially harmful nonself molecules and cells from the body. The immune system also has the capacity to recognize and destroy abnormal cells that derive from host tissues. Any molecule capable of being recognized by the immune system is considered an antigen (Ag). – Merck Manual

Excerpts:

“We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles.”

“We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.”

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  • June 26, 2023

Excerpts:
“As a result of these pieces of evidence (epidemiological, clinical and preclinical data) pointing to a potential causal association between early ABA (aluminum-based adjuvants) exposure and increased ASD risk, new hypotheses regarding neurological and immunological consequences of ABA-containing vaccines and novel clinical strategies (i.e., postponing of ABA-containing vaccines and replacement of ABAs with calcium phosphate are now being considered.“

“Our review presents the lack of fundamental scientific data demonstrating that Al adjuvants are safe and do not induce any long-term side effects. It also supports further investigation related to the effects of early Al adjuvant exposures occurring in combination with genetic susceptibility factors, including autophagy, immune and inflammation process genes. As accumulating evidence shows that modulating the levels of autophagy may increase the risk of NDDs, such studies will elucidate a new etiology for these complex disorders and contribute to develop potential new diagnostic and therapeutic tools.”

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  • August 31, 2022

Excerpts:

“Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms.”

“Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.”

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  • December 7, 2021

Press Release from Harvard Magazine:

“Inflammation link for autism
A neuroimaging study has shown that the brains of young men with autism spectrum disorder have low levels of translocator protein, a substance that appears to play a role in inflammation and metabolism.

This discovery by a team of HMS researchers at Massachusetts General Hospital provides an important insight into the possible origins of autism spectrum disorder.

This developmental disorder, which affects one in fifty-nine children in the United States, emerges in early childhood and is characterized by difficulty communicating and interacting with others. Although the cause is unknown, growing evidence has linked it to neuroinflammation.

One sign of neuroinflammation is elevated levels of translocator protein, which can be measured in the brain using positron-emission tomography and anatomic magnetic resonance imaging.

The research team used these imaging tools to scan the brains of fifteen young adult males with the disorder. The group included both high- and low-functioning participants with varying degrees of intellectual ability. As a control, the team scanned the brains of eighteen non-autistic young men of similar age.

The scans showed that the brains of the young men with the disorder had lower levels of the protein, compared with the brains of non-autistic participants. In fact, those participants with the most severe symptoms of the disorder tended to have the lowest expression of the protein.

The brain regions found to have low expression of the protein have previously been linked to autism spectrum disorder and are thought to govern social and cognitive capacities such as processing emotions, interpreting facial expressions, and empathy.

The researchers point out that the translocator protein has multiple complex roles, some of which promote brain health. Adequate levels of the protein are, for example, necessary for normal functioning of mitochondria. Earlier research has linked malfunctioning mitochondria in brain cells to autism spectrum disorder.

Zürcher NR et al., Molecular Psychiatry, February 2020

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  • February 19, 2020

Except:
“There is a growing body of work to support the role of inflammatory cytokines in ASD. An emerging focus of research into the etiology of ASD has suggested neuroinflammation as one of the major candidates underlying the biologica model [5]. Plasma levels of IL-1β, IL-6 and IL-8 were increased in children with ASD and correlated with regressive autism, as well as impaired communication and aberrant behavior [6-8]. Vargas [9] showed an active neuroinflammatory process in the cerebral cortex, white matter, and in the cerebellum of autistic patients. Immunocytochemichal studies showed marked activation of microglia [5].”

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  • January 1, 2019

Excerpt:
“In this review article, we examine the connections between early disruption of the developing microbiome and gastrointestinal tract function, with particular regard to susceptibility to autism. The biological mechanisms that accompany individuals with autism are reviewed in this manuscript including immune system dysregulation, inflammation, oxidative stress, metabolic and methylation abnormalities as well as gastrointestinal distress.”

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  • August 15, 2018

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

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

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