Immunological and autoimmune considerations of Autism Spectrum Disorders

Gesundheit, Benjamin; Rosenzweig, Joshua P.; Naor, David; Lerer, Bernard; Zachor, Ditza A.; Procházka, Václav; Melamed, Michal L.; Kristt, Donald A.; Steinberg, Avraham; Shulman, Cory; Hwang, Paul A.; Koren, Gideon; Walfisch, Asnat; Passweg, Jakob; Snowden, John A.; Tamouza, Ryad; Leboyer, Marion; Farge‐Bancel, Dominique; Ashwood, Paul

doi:10.1016/j.jaut.2013.05.005

Cited by 170 publications

(117 citation statements)

References 67 publications

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“…Given that PLK2 induction resulted in dendritic spine dysmorphogenesis,42 downregulation of miR‐219‐5p might contributed to synaptic dysfunction in ASD pathophysiology. Although ASD is a neurodevelopmental disorder, there are several comorbidities, such as gastrointestinal distress and immune dysregulation, observed in patients with ASD 43. Moreover, a gut‐microbiome‐brain connection was found to contribute to ASD pathogenesis,16 further suggesting that ASD is a systemic disorder caused by both genetic and environmental factors.…”

Section: Discussionmentioning

confidence: 99%

Maternal immune activation alters brain microRNA expression in mouse offspring

Sunwoo

Jeon²,

Moon

et al. 2018

Ann Clin Transl Neurol

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ObjectiveMaternal immune activation (MIA) is associated with an increased risk of autism spectrum disorder (ASD) in offspring. Herein, we investigate the altered expression of microRNAs (miRNA), and that of their target genes, in the brains of MIA mouse offspring.MethodsTo generate MIA model mice, pregnant mice were injected with polyriboinosinic:polyribocytidylic acid on embryonic day 12.5. We performed miRNA microarray and mRNA sequencing in order to determine the differential expression of miRNA and mRNA between MIA mice and controls, at 3 weeks of age. We further identified predicted target genes of dysregulated miRNAs, and miRNA‐target interactions, based on the inverse correlation of their expression levels.ResultsMice prenatally subjected to MIA exhibited behavioral abnormalities typical of ASD, such as a lack of preference for social novelty and reduced prepulse inhibition. We found 29 differentially expressed miRNAs (8 upregulated and 21 downregulated) and 758 differentially expressed mRNAs (542 upregulated and 216 downregulated) in MIA offspring compared to controls. Based on expression levels of the predicted target genes, 18 downregulated miRNAs (340 target genes) and three upregulated miRNAs (60 target genes) were found to be significantly enriched among the differentially expressed genes. miRNA and target gene interactions were most significant between mmu‐miR‐466i‐3p and Hfm1 (ATP‐dependent DNA helicase homolog), and between mmu‐miR‐877‐3p and Aqp6 (aquaporin 6).InterpretationOur results provide novel information regarding miRNA expression changes and their putative targets in the early postnatal period of brain development. Further studies will be needed to evaluate potential pathogenic roles of the dysregulated miRNAs.

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Section: Discussionmentioning

confidence: 99%

Maternal immune activation alters brain microRNA expression in mouse offspring

Sunwoo

Jeon²,

Moon

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

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“…Schizophrenia and autism share many immune similarities, including a subset of patients with an etiology based in maternal infection and immune activation (Bauman et al, 2014;Boksa, 2010;Brown et al, 2004a;Meyer et al, 2005Meyer et al, , 2007Patterson, 2009;Urakubo et al, 2001). Further lending credence to this association are numerous studies showing that a significant risk factor for autism is a family history of autoimmune disease (Brimberg et al, 2013;Gesundheit et al, 2013;Gottfried et al, 2015;Wu et al, 2015), alongside direct genetic evidence that links ASD and schizophrenia (Cantor and Geschwind, 2008;Ellis et al, 2016;Zhou et al, 2016). Despite the differences between these two disorders, the similarities between them are such that results from animal models like the MIA model may be overlapping and confounded (Bauman et al, 2014;Young et al, 2016).…”

Section: Asd As An Autoimmune Disordermentioning

confidence: 97%

The Role of the Immune System in Autism Spectrum Disorder

Meltzer

Water

2016

Neuropsychopharmacol

387

293

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Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment.

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“…In the present study, we showed that deficiencies in salivary sIgA levels were strongly associated with severe impairments in some clinical features in ASD group, strengthening the association between immune dysfunction and at least a subset of behaviors associated with autism. This association has been vastly explored by researchers who reported increased pro-inflammatory markers as the most consistent observation among the immunological findings in ASD [29,30] . As noted, many of these studies highlight a connection between immune dysregulation and more impaired behaviors.…”

Section: Discussionmentioning

confidence: 86%

Salivary IgA Correlate with Recurrent Respiratory Infections and Hyperreactivity in Children with Autism

Furland

Sindelar²

2016

International Journal of Neurology Research

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AIM: Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted interests and behaviors. Accumulating evidence suggests that dysregulation of the immune system may be involved in the pathophysiology of ASD. The aim of the study was to assess if the severity of clinical and behavioral parameters of autistic children was associated with low levels of secretory IgA (sIgA) in saliva. We hypothesized that a decreased immune response in children with autism would decrease the levels of sIgA, as is the predominant antibody isotype in saliva and a marker of mucosal immunity. MATERIALS AND METHODS: Saliva samples were obtained from 3-10 year-old children with ASD and age-matched typically developing Caucasian children from Patagonia region, Argentina. RESULTS AND CONCLUSIONS: Autistic children with reduced levels of salivary IgA had a higher incidence of upper respiratory diseases compared to the controls. The reduction in sIgA levels also correlated inversely with the severity of the behavioral disorders. The patients with the most severe impairment in autism-related behaviors had the lowest levels of sIgA in the cohort studied. These findings suggest that sIgA could be an early indicator and possibly a biomarker of the dysregulation of the immune system in some children with autism. The characterization of immunological parameters in ASD has important implications for detection of a subset of individuals with ASD, and should be considered when designing therapeutic strategies to treat core symptoms and behavioral impairments of ASD.

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Immunological and autoimmune considerations of Autism Spectrum Disorders

Cited by 170 publications

References 67 publications

Maternal immune activation alters brain microRNA expression in mouse offspring

Maternal immune activation alters brain microRNA expression in mouse offspring

The Role of the Immune System in Autism Spectrum Disorder

Salivary IgA Correlate with Recurrent Respiratory Infections and Hyperreactivity in Children with Autism

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