Article

Autoantibodies in Autism Spectrum Disorders (ASD)

Division of Rheumatology, Allergy and Clinical Immunology, UC Davis, Davis, CA 95616, USA.
Annals of the New York Academy of Sciences (Impact Factor: 4.31). 07/2007; 1107(1):79-91. DOI: 10.1196/annals.1381.009
Source: PubMed

ABSTRACT Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders defined behaviorally by abnormalities in social, verbal, and nonverbal communication. The etiologies of ASD are unknown, likely to be the result of a variety of numerous genetic, neurological, environmental, and immunological interactions that lead to a general behavioral phenotype defined as ASD. This review will focus on the various immune system anomalies, in particular, autoantibodies, which have been reported in subjects with ASD. In addition, we will discuss recent studies performed by our group concerning the presence of autoantibodies directed against neural antigens, which are observed in patients with ASD.

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    • "Moreover, the plasma level of oxytocin, a hormone that plays an important role in the regulation of repetitive behaviors, is significantly altered in individuals with behavioral and neurodevelopmental problems related to ASD (Alabdali et al., 2014; Hammock et al., 2012). The presence of immunological markers, such as inflammatory cytokines and autoantibodies, also correlate with the underlying features of ADS (Ross et al., 2013; Wills et al., 2007). Increased production of proinflammatory cytokines such as transforming growth factor alpha 1 (TGF-␣1), tumor necrosis factor alpha (TNF␣), interleukin 6 (IL-6), and interleukin 10 (IL- 10) is frequently observed in autistic subjects and can be measured from both brain tissues and blood samples (Ross et al., 2013; Vargas et al., 2005). "
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    ABSTRACT: Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders that is among the most severe in terms of prevalence, morbidity and impact to the society. It is characterized by complex behavioral phenotype and deficits in both social and cognitive functions. Although the exact cause of ASD is still not known, the main findings emphasize the role of genetic and environmental factors in the development of autistic behavior. Environmental factors are also likely to interact with the genetic profile and cause aberrant changes in brain growth, neuronal development, and functional connectivity. The past few years have seen an increase in the prevalence of ASD, as a result of enhanced clinical tests and diagnostic tools. Despite growing evidence for the involvement of endogenous biomarkers in the pathophysiology of ASD, early detection of this disorder remains a big challenge. This paper describes the main behavioral and cognitive features of ASD, as well as the symptoms that differentiate autism from other developmental disorders. An attempt will be made to integrate all the available evidence which point to reduced brain connectivity, mirror neurons deficits, and inhibition-excitation imbalance in individuals with ASD. Finally, this review discusses the main factors involved in the pathophysiology of ASD, and illustrates some of the most important markers used for the diagnosis of this debilitating disorder. Copyright © 2015. Published by Elsevier Ltd.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 04/2015; 43. DOI:10.1016/j.ijdevneu.2015.04.003 · 2.92 Impact Factor
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    • "In recent years, several studies reported the presence of circulating IgG autoantibodies that react with components of the central nervous system (CNS) in individuals with Autism Spectrum Disorder (ASD) (Enstrom et al., 2009), a neurodevelopmental disease characterized by deficits in social reciprocity and communication, as well as by unusually restricted interests and repetitive behaviors (American Psychiatric Association, 2013). These autoantibodies, displaying a significantly lower prevalence in population controls compared to autistic individuals (Wills et al., 2009; Goines et al., 2011), seemingly target different brain regions, including thalamus , hypothalamus, caudate nucleus, cerebral cortex, and putamen , but most consistently the cerebellum (Cabanlit et al., 2007; Wills et al., 2007, 2011). Cerebellar specific IgG autoantibodies, initially estimated approximately 52 kDa in size and directed mainly against calretinin-positive GABAergic Golgi cells, were identified by Western Blot analysis in plasma from children with ASD (Cabanlit et al., 2007; Wills et al., 2011). "
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    ABSTRACT: Circulating 45 and 62 kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73 kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N = 355), their unaffected siblings (N = 142) and mothers (N=333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62 kDa antibodies are correlated with autism severity: the 45 kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62 kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P<0.05). On the other hand, maternal 37, 39 and 73 kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P<0.05). Presence of the 62 kDa autoAb in the child is significantly associated with presence of the 39 and/or 73 kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for anti-brain antibodies in autism while demonstrating their familial clustering.
    Brain Behavior and Immunity 01/2014; DOI:10.1016/j.bbi.2013.12.020 · 6.13 Impact Factor
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    • "Hertz-Picciotto [35] noted the probable relationship between autism and the immune dysfunction associated with autism. The presence of brain autoantibodies in a significant number of autistic children [36] [37] [38] [39] [40] suggests the pathogenic role of autoimmunity in those autistic patients. This is true not just for children with autism, but also for their family members [41]. "
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    ABSTRACT: Autism is a heterogeneous group of life-long neurologic problems that begin in childhood. Success in efforts to understand and treat autism has been mostly elusive. The role of autoimmunity in autism has gained recognition both for associated systemic autoimmune disease and the presence of brain autoantibodies in autistic children and their family members. There is an acknowledged genetic susceptibility to autism--most notably allotypes of complement C4. C4 defects are associated with several autoimmune diseases and also confer susceptibility to mycobacterial infections. Mycobacterium avium ss. paratuberculosis (MAP) causes an enteric inflammatory disease in ruminant animals (Johne's disease) and is the putative cause of the very similar Crohn's disease in humans. Humans are widely exposed to MAP in food and water. MAP has been also linked to ulcerative colitis, irritable bowel syndrome, sarcoidosis, Blau syndrome, autoimmune (Type 1) diabetes, Hashimoto's thyroiditis and multiple sclerosis. Environmental agents are thought to trigger autism in the genetically at risk. Molecular mimicry is the proposed mechanism by which MAP is thought to trigger autoantibodies. Autoantibodies to brain myelin basic protein (MBP) is a common feature of autism. This article considers the subset of autoimmunity-related autism patients and postulates that MAP, through molecular mimicry to its heat shock protein HSP65, triggers autism by stimulating antibodies that cross react with myelin basic protein (MBP).
    Medical Hypotheses 09/2011; 77(6):977-81. DOI:10.1016/j.mehy.2011.08.024 · 1.07 Impact Factor
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