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.
    Science of The Total Environment 07/2015; 536:245-251. DOI:10.1016/j.scitotenv.2015.07.024 · 4.10 Impact Factor
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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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    ABSTRACT: Autism spectrum disorders (ASD) are a group of neuro-developmental disorders in early childhood which are defined by social difficulties, communication deficits and repetitive or restrictive interests and behaviours. The etiology of ASD remains poorly understood. Much research has shown that children with ASD suffer from immunological dysfunction. This article reviews the current research progress on immunological dysfunction in children with ASD, including abnormalities in immune cells, antibodies, complements, cytokines, major histocompatibility complex and their potential association with ASD, and explores the impacts of maternal immunological activation on the immune dysfunction of children with ASD.
    Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 12/2014; 16(12):1289-1293. DOI:10.7499/j.issn.1008-8830.2014.12.023
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    • "Several epidemiological studies have reported immune dysregulation in children with ASD and their mothers, suggesting a role for the immune system in the pathology of the disorder [5-9]. Several research groups have found that individuals with ASD have increased neuroinflammation in brain tissues [10-12], imbalances in immunoglobulins, including increased levels of plasma IgG4 [13], reduced levels of total IgG [14] or reduced levels of IgG and IgM [15,16], and imbalances in cytokine/chemokine levels [17,18]. However, the mechanisms through which immune dysfunction may contribute to the etiology of autism are not understood [19]. "
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    ABSTRACT: Biologic markers of infection and inflammation have been associated with Autism Spectrum Disorders (ASD) but prior studies have largely relied on specimens taken after clinical diagnosis. Research on potential biologic markers early in neurodevelopment is required to evaluate possible causal pathways and screening profiles. To investigate levels of cytokines and chemokines in newborn blood specimens as possible early biologic markers for autism. We conducted a population-based case-control study nested within the cohort of infants born from July 2000 to September 2001 to women who participated in the prenatal screening program in Orange County, California, USA. The study population included children ascertained from the California Department of Developmental Services with Autism Spectrum Disorder (ASD, n = 84), or developmental delay but not ASD (DD, n = 49), and general population controls randomly sampled from the birth certificate files and frequency matched to ASD cases on sex, birth month and birth year (GP, n = 159). Cytokine and chemokine concentrations were measured in archived neonatal blood specimens collected for routine newborn screening. Cytokines were not detected in the vast majority of newborn samples regardless of case or control status. However, the chemokine monocyte chemotactic protein-1 (MCP-1) was elevated and the chemokine Regulated upon Activation Normal T-Cell Expressed and Secreted (RANTES) was decreased in ASD cases compared to GP controls. The chemokines macrophage inflammatory protein-1alpha (MIP-1α) and RANTES were decreased in children with DD compared to GP controls. Measurement of immune system function in the first few days of life may aid in the early identification of abnormal neurodevelopment and shed light on the biologic mechanisms underlying normal neurodevelopment.
    Journal of Neuroinflammation 06/2014; 11(1):113. DOI:10.1186/1742-2094-11-113 · 5.41 Impact Factor
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