Is autism an autoimmune disease?

Department of Internal Medicine, Division of Rheumatology, and UC Davis M.I.N.D. Institute, University of California, Davis, CA 95616, USA.
Autoimmunity Reviews (Impact Factor: 7.93). 12/2004; 3(7-8):557-62. DOI: 10.1016/j.autrev.2004.07.036
Source: PubMed


Autism spectrum disorder (ASD) is a spectrum of behavioral anomalies characterized by impaired social interaction and communication, often accompanied by repetitive and stereotyped behavior. The condition manifests within the first 3 years of life and persists into adulthood. There are numerous hypotheses regarding the etiology and pathology of ASD, including a suggested role for immune dysfunction. However, to date, the evidence for involvement of the immune system in autism has been inconclusive. While immune system abnormalities have been reported in children with autistic disorder, there is little consensus regarding the nature of these differences which include both enhanced autoimmunity and reduced immune function. In this review, we discuss current findings with respect to immune function and the spectrum of autoimmune phenomena described in children with ASD.

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Available from: Judy Van de Water, Oct 13, 2015
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    • "Autoimmune autistic disorder is proposed as a major subset of autism (118), and autoimmunity may play a role in the pathogenesis of language and social developmental abnormalities in a subset of children with these disorders (119). There are many autoantibodies found in the nervous system of children with ASD who have a high level of brain antibodies (120, 121). These can be measured as biomarkers in this subset of ASD patients. "
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    ABSTRACT: Autism spectrum disorders (ASDs) are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression, and measures of the body's metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.
    Frontiers in Psychiatry 08/2014; 5:100. DOI:10.3389/fpsyt.2014.00100
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    • "Autism spectrum disorders are characterized by language impairment, restricted interests, stereotypic motor behaviors, hyperactivity, sensory disturbances and self injury [7]. It is also associated with seizure disorder [8], gastrointestinal disturbances [9] and autoimmune disorders in some patients [10]. The methylene tetrahydrofolate reductase (MTHFR) gene codes for an essential enzyme in folate metabolism. "
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    ABSTRACT: Classical autism belongs to a group of heterogeneous neurobehavioral disorders known as autism spectrum disorders (ASDs) characterized by abnormalities in social interaction, impaired communication, and repetitive stereotypic behaviors. Overall, there is an increased risk of ASDs associated with common mutations affecting the folate/methylation cycle. This study aimed at identification of the C677T polymorphic genotypes of MTHFR gene among the Egyptian children with autism and to correlate them with different phenotypes.
    Egyptian Journal of Medical Human Genetics 06/2014; 15(4). DOI:10.1016/j.ejmhg.2014.05.004
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    • "Indeed, it has been suggested that systematic abnormalities in ASD, such as mitochondrial dysfunction, may arise from environmental triggers14 in genetically sensitive subpopulations.18, 19 This notion is strongly supported by a recent study of dizygotic twins, which estimated that the environment contributed a greater percent of the risk of developing autistic disorder (55%) as compared with genetic factors (37%) with these factors contributing about equally for the broader ASD diagnosis.14 Mitochondria are central to this concept as polymorphisms in mitochondrial genes can result in susceptibility to disease20, 21 and mitochondrial dysfunction can result from environmental exposures that have been implicated in the development of ASD such as heavy metals,22, 23, 24, 25 chemicals,26 polychlorinated biphenyls27 or pesticides28, 29 as well as physiological abnormalities associated with ASD such as elevated tumor necrosis factor α,30, 31, 32 glutathione deficiency33 and oxidative stress.34 "
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    ABSTRACT: Research studies have uncovered several metabolic abnormalities associated with autism spectrum disorder (ASD), including mitochondrial disease (MD) and abnormal redox metabolism. Despite the close connection between mitochondrial dysfunction and oxidative stress, the relation between MD and oxidative stress in children with ASD has not been studied. Plasma markers of oxidative stress and measures of cognitive and language development and ASD behavior were obtained from 18 children diagnosed with ASD who met criteria for probable or definite MD per the Morava et al. criteria (ASD/MD) and 18 age and gender-matched ASD children without any biological markers or symptoms of MD (ASD/NoMD). Plasma measures of redox metabolism included reduced free glutathione (fGSH), oxidized glutathione (GSSG), the fGSH/GSSG ratio and 3-nitrotyrosine (3NT). In addition, a plasma measure of chronic immune activation, 3-chlorotyrosine (3CT), was also measured. Language was measured using the preschool language scale or the expressive one-word vocabulary test (depending on the age), adaptive behaviour was measured using the Vineland Adaptive Behavior Scale (VABS) and core autism symptoms were measured using the Autism Symptoms Questionnaire and the Social Responsiveness Scale. Children with ASD/MD were found to have lower scores on the communication and daily living skill subscales of the VABS despite having similar language and ASD symptoms. Children with ASD/MD demonstrated significantly higher levels of fGSH/GSSG and lower levels of GSSG as compared with children with ASD/NoMD, suggesting an overall more favourable glutathione redox status in the ASD/MD group. However, compare with controls, both ASD groups demonstrated lower fGSH and fGSH/GSSG, demonstrating that both groups suffer from redox abnormalities. Younger ASD/MD children had higher levels of 3CT than younger ASD/NoMD children because of an age-related effect in the ASD/MD group. Both ASD groups demonstrated significantly higher 3CT levels than control subjects, suggesting that chronic inflammation was present in both groups of children with ASD. Interestingly, 3NT was found to correlate positively with several measures of cognitive function, development and behavior for the ASD/MD group, but not the ASD/NoMD group, such that higher 3NT concentrations were associated with more favourable adaptive behaviour, language and ASD-related behavior. To determine whether difference in receiving medications and/or supplements could account for the differences in redox and inflammatory biomarkers across ASD groups, we examined differences in medication and supplements across groups and their effect of redox and inflammatory biomarkers. Overall, significantly more participants in the ASD/MD group were receiving folate, vitamin B12, carnitine, co-enzyme Q10, B vitamins and antioxidants. We then determined whether folate, carnitine, co-enzyme Q10, B vitamins and/or antioxidants influenced redox or inflammatory biomarkers. Antioxidant supplementation was associated with a significantly lower GSSG, whereas antioxidants, co-enzyme Q10 and B vitamins were associated with a higher fGSH/GSSG ratio. There was no relation between folate, carnitine, co-enzyme Q10, B vitamins and antioxidants with 3NT, 3CT or fGSH. Overall, our findings suggest that ASD/MD children with a more chronic oxidized microenvironment have better development. We interpret this finding in light of the fact that more active mitochondrial can create a greater oxidized microenvironment especially when dysfunctional. Thus, compensatory upregulation of mitochondria which are dysfunctional may both increase activity and function at the expense of a more oxidized microenvironment. Although more ASD/MD children were receiving certain supplements, the use of such supplements were not found to be related to the redox biomarkers that were related to cognitive development or behavior in the ASD/MD group but could possibly account for the difference in glutathione metabolism noted between groups. This study suggests that different subgroups of children with ASD have different redox abnormalities, which may arise from different sources. A better understanding of the relationship between mitochondrial dysfunction in ASD and oxidative stress, along with other factors that may contribute to oxidative stress, will be critical to understanding how to guide treatment and management of ASD children. This study also suggests that it is important to identify ASD/MD children as they may respond differently to specific treatments because of their specific metabolic profile.
    Translational Psychiatry 06/2013; 3(6):e273. DOI:10.1038/tp.2013.51 · 5.62 Impact Factor
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