Increased IgG4 levels in children with autism disorder. Brain Behav Immun

Department of Medical Microbiology and Immunology, 2805, 50th Street, Wet lab building, Sacramento, CA 95817, USA.
Brain Behavior and Immunity (Impact Factor: 5.89). 03/2009; 23(3):389-95. DOI: 10.1016/j.bbi.2008.12.005
Source: PubMed


Accumulating evidence indicates that immune dysfunction is associated with autism disorders in a significant subset of children. Previous reports have shown abnormal immunoglobulin (Ig) levels, including an increased presence of autoreactive antibodies in the circulation of individuals with autism. As IgG is the predominant antibody isotype in circulation, we expected that an altered immune response could result in an abnormal IgG subclass profile in children with autism. We examined circulating plasma levels of IgG1, IgG2, IgG3, and IgG4 in 241 children from the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a large epidemiologic case-control investigation, including 114 children who meet full criteria for autism disorder (AU), 96 typically developing control children (TD) from a randomly selected sample of the general population, and 31 children with developmental delays (DD). We report significantly increased levels of the IgG4 subclass in children with AU compared with TD control children (p=0.016) and compared with DD controls (p=0.041). These results may suggest an underlying immunological abnormality in AU subjects resulting in elevated IgG4 production. Further investigation is necessary to elucidate the relationship between immunological findings and behavioral impairments in autism.

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    • "Both long-term and short-term exposures to ambient air pollutants have been shown to stimulate oxidative stress and inflammation in humans, which may also affect neurologic development (Block and Calderon-Garciduenas, 2009; Calderon-Garciduenas et al., 2009). Studies have also shown that inflammation may contribute to the pathogenesis of ASD (Enstrom et al., 2009; Li et al., 2009). Thus, inflammation may serve as a link between ASD risk and ambient air pollutant exposure . "
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    ABSTRACT: Prenatal and perinatal exposures to air pollutants have been shown to adversely affect birth outcomes in offspring and may contribute to prevalence of autism spectrum disorder (ASD). For this ecologic study, we evaluated the association between ASD prevalence, at the census tract level, and proximity of tract centroids to the closest industrial facilities releasing arsenic, lead or mercury during the 1990s. We used 2000 to 2008 surveillance data from five sites of the Autism and Developmental Disabilities Monitoring (ADDM) network and 2000 census data to estimate prevalence. Multi-level negative binomial regression models were used to test associations between ASD prevalence and proximity to industrial facilities in existence from 1991 to 1999 according to the US Environmental Protection Agency Toxics Release Inventory (USEPA-TRI). Data for 2489 census tracts showed that after adjustment for demographic and socio-economic area-based characteristics, ASD prevalence was higher in census tracts located in the closest 10th percentile compared of distance to those in the furthest 50th percentile (adjusted RR=1.27, 95% CI: (1.00, 1.61), P=0.049). The findings observed in this study are suggestive of the association between urban residential proximity to industrial facilities emitting air pollutants and higher ASD prevalence. Copyright © 2015 Elsevier B.V. All rights reserved.
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    • "One study reported that children with autism have reduced levels of plasma IgG and IgM which also correlated with increased behavioral severity (Heuer et al. 2011). Other studies have reported increases in serum proteins attributed mostly to increases in albumin; however, IgG, specifically IgG2 and IgG4 were also seen elevated in individuals with ASD and these increases in immunoglobulin correlated with behavioral abnormalities (Croonenberghs et al. 2002;Enstrom et al. 2009a). Autoantibodies to various and diverse targets have been reported in children with autism and could point to cellular damage that may be involved in increasing inflammation, revealing antigens otherwise hidden and/or epitope spreading (Onore et al. 2012). "
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    ABSTRACT: Autism spectrum disorders (ASD) are developmental disorders characterized by behavioral deficits in verbal and nonverbal communication as well as social interactions, and are accompanied by repetitive or stereotyped behaviors and interests. Numerous studies over the last forty years have recognized altered immune responses in individuals with ASD; concurrently basic research has highlighted the myriad of neuroimmune interactions and the cross talk that occurs between nervous and immune systems. Neuroinflammation, particularly in the cerebellum, has been found in post mortem brain tissues from individuals with ASD and is characterized by the presence of profound glia activation processes. This and altered gene expression profiles indicating perturbed immune suggest a contributing role for immunological systems in the pathology of ASD. Peripheral immune abnormalities have also been found; shifts in both direction of Th1 and Th2 skewing have been reported as well as autoantibody production, increased NK cell activation, T cell responses and monocyte cell function overwhelmingly suggesting the presence of immune dysfunction in individuals with ASD. Many of these findings are associated with worsening behavioral scores, suggesting treatment of immune function could be useful in alleviating symptoms associated with ASD. Immune activation in utero is also associated with an increased risk of the child for having a diagnosis of ASD, where increased cytokine production in the offspring is directly linked to changes in offspring behavior. In addition to peripheral changes, brain and CSF immune variations in ASD are reported as well as an increase in gastrointestinal/mucosal dysfunction which has led to an increased interest in exploring the gut-brain-immune connections and its role in ASD. Further research in neuroimmune interactions may bring further insight and elicit new therapeutic tools for ASD.
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    • "。 与 IL-4 一样,IFN-γ 不穿过胎盘,产妇血清水平与 胎儿暴露于细胞因子的关系也尚不清楚。 3 免疫球蛋白 与 ASD 中 B 细 胞 的 变 化 一 样,ASD 中 免 疫 球蛋白水平的研究结果亦不一致。有研究发现孤 独症患儿血清 IgG 的一个亚型 IgG4 显著增加,而 IgG1、IgG2、IgG3 没有改变 [36] "
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