Autoantibodies in Autism Spectrum Disorders (ASD)

Division of Rheumatology/Allergy/Clinical Immunology, University of California, Davis, Davis, California, United States
Annals of the New York Academy of Sciences (Impact Factor: 4.38). 07/2007; 1107(1):79-91. DOI: 10.1196/annals.1381.009
Source: PubMed


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.
    Full-text · Article · Apr 2015 · International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience
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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.
    Full-text · Article · Jan 2014 · Brain Behavior and Immunity
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    • "Furthermore, elevated anti-phospholipid antibodies are associated with increased impairments in a number of clinical cognitive and behavioral measures such as stereotypy, hyperactivity, and communication. Together with previous studies in the field demonstrating the increased presence of autoantibodies in children with ASD, this study adds further support for a possible role for autoimmune phenomena in the pathogenesis of ASD [25]. Several previous studies have shown that increased anti-phospholipid antibodies are present in a number of neuropsychiatric conditions; however, it is currently unclear what, if any, pathologic significance these anti-phospholipid antibodies have in behavioral disorders including ASD. "
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    ABSTRACT: Autism spectrum disorders (ASD) are characterized by impairments in communication, social interactions, and repetitive behaviors. While the etiology of ASD is complex and likely involves the interplay of genetic and environmental factors, growing evidence suggests that immune dysfunction and the presence of autoimmune responses including autoantibodies may play a role in ASD. Anti-phospholipid antibodies are believed to occur from both genetic and environmental factors and have been linked to a number of neuropsychiatric symptoms such as cognitive impairments, anxiety, and repetitive behaviors. In the current study, we investigated whether there were elevated levels of anti-phospholipid antibodies in a cross-sectional analysis of plasma of young children with ASD compared to age-matched typically developing (TD) controls and children with developmental delays (DD) other than ASD. We found that levels of anti-cardiolipin, β 2-glycoprotein 1, and anti-phosphoserine antibodies were elevated in children with ASD compared with age-matched TD and DD controls. Further, the increase in antibody levels was associated with more impaired behaviors reported by parents. This study provides the first evidence for elevated production of anti-phospholipid antibodies in young children with ASD and provides a unique avenue for future research into determining possible pathogenic mechanisms that may underlie some cases of ASD.
    Full-text · Article · Sep 2013 · Mediators of Inflammation
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