Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders

Nanea, Department of Epidemiology, Institute of Public Health, bNational Centre for Register-Based Research, and eInstitute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
PEDIATRICS (Impact Factor: 5.47). 09/2009; 124(2):687-94. DOI: 10.1542/peds.2008-2445
Source: PubMed


Recent studies suggest that familial autoimmunity plays a part in the pathogenesis of ASDs. In this study we investigated the association between family history of autoimmune diseases (ADs) and ASDs/infantile autism. We perform confirmatory analyses based on results from previous studies, as well as various explorative analyses.
The study cohort consisted of all of the children born in Denmark from 1993 through 2004 (689 196 children). Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry. Information on ADs in parents and siblings of the cohort members was obtained from the Danish National Hospital Register. The incidence rate ratio of autism was estimated by using log-linear Poisson regression.
A total of 3325 children were diagnosed with ASDs, of which 1089 had an infantile autism diagnosis. Increased risk of ASDs was observed for children with a maternal history of rheumatoid arthritis and celiac disease. Also, increased risk of infantile autism was observed for children with a family history of type 1 diabetes.
Associations regarding family history of type 1 diabetes and infantile autism and maternal history of rheumatoid arthritis and ASDs were confirmed from previous studies. A significant association between maternal history of celiac disease and ASDs was observed for the first time. The observed associations between familial autoimmunity and ASDs/infantile autism are probably attributable to a combination of a common genetic background and a possible prenatal antibody exposure or alteration in fetal environment during pregnancy.

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Available from: Hjördís Osk Atladóttir, Apr 12, 2014
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    • "Epidemiological studies demonstrating an association between family history of autoimmune diseases (Table 1) and ASD [18]. "
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    ABSTRACT: Recent studies of Autism Spectrum Disorders (ASD) highlight hyperactivity of the immune system, irregular neuronal growth and increased size and number of microglia. Though the small sample size in many of these studies limits extrapolation to all individuals with ASD, there is mounting evidence of both immune and nervous system related pathogenesis in at least a subset of patients with ASD. Given the disturbing rise in incidence rates for ASD, and the fact that no pharmacological therapy for ASD has been approved by the Food and Drug Administration (FDA), there is an urgent need for new therapeutic options. Research in the therapeutic effects of mesenchymal stem cells (MSC) for other immunological and neurological conditions has shown promising results in preclinical and even clinical studies. MSC have demonstrated the ability to suppress the immune system and to promote neurogenesis with a promising safety profile. The working hypothesis of this paper is that the potentially synergistic ability of MSC to modulate a hyperactive immune system and its ability to promote neurogenesis make it an attractive potential therapeutic option specifically for ASD. Theoretical mechanisms of action will be suggested, but further research is necessary to support these hypothetical pathways. The choice of tissue source, type of cell, and most appropriate ages for therapeutic intervention remain open questions for further consideration. Concern over poor regulatory control of stem cell studies or treatment, and the unique ethical challenges that each child with ASD presents, demands that future research be conducted with particular caution before widespread use of the proposed therapeutic intervention is implemented.
    Medical Hypotheses 12/2014; 84(3). DOI:10.1016/j.mehy.2014.12.016 · 1.07 Impact Factor
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    • "These observations are in agreement with increasing evidences suggesting that immune activation during prenatal life is a risk factor for ASD (Easson and Woodbury- Smith, 2014). Notably, immune activation and inflammation are involved in the pathogenesis of recurrent spontaneous abortion and autoimmune disorders: both these phenomena are more frequent in mothers of ASD children (Funderburk et al., 1983; Comi et al., 1999; Croen et al., 2005; Atladóttir et al., 2009; Altevogt et al., 2008; Sweeten et al., 2003). "
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    ABSTRACT: HLA-G expressed by the trophoblast ligates KIR molecules expressed by maternal NK cells at the uterine fetal/maternal interface: this interaction is involved in generating immune tolerance during pregnancy. A 14-bp insertion in the HLA-G 3′-UTR associates with significantly reduced levels of both HLA-G mRNA and soluble HLA-G, thus hampering the efficacy of HLA-G-mediated immune tolerance during pregnancy. Because prenatal immune activation is suggested to play an important role in the onset of autistic spectrum disorders (ASD) we performed an in-depth evaluation of HLA-G polymorphisms in a well-characterized cohort of Italian families of ASD children. Results showed that frequency of both homozygous 14bp+/14bp+ genotype and 14bp+ allele was significantly higher in ASD children and their mothers compared to controls (p < 0.05 in all cases); analysis of the frequency of transmission of the 14bp+ allele from parents to ASD children and their non-ASD siblings showed that the 14bp+ allele was more frequently transmitted (T) to ASD children, whereas it was preferentially not transmitted (NT) to the non-ASD siblings (overall discrepancy: p = 0.02; OR: 2.6, 95% CI: 1.1-6.4). Results herein suggest that HLA-G polymorphisms are associated with ASD development, possibly as a consequence of prenatal immune activation. These data infer that the immune alterations seen in ASD are associated with the maternal-fetal interaction alone, and reinforce the observation that different genetic backgrounds characterize ASD children and their non-ASD siblings.
    Brain Behavior and Immunity 10/2014; 44. DOI:10.1016/j.bbi.2014.10.002 · 5.89 Impact Factor
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    • "Variables reflecting parental age, parental psychiatric history , gestational age, birth weight, parental history of autoimmune disease, and number of live births, obstetric complications, and family socioeconomic status (a combination of parental income and highest level of education) were available in the Danish registers and were chosen a priori based on the literature (Atladottir et al. 2009, 2010; Burstyn et al. 2010; Daniels et al. 2008; Durkin et al. 2010; Giarelli et al. 2010; Larsson 2005; Schendel and Bhasin 2008). Gestational age was given in days from self-reported last menstrual period, and confirmed using an ultrasound date if the last menstrual period was uncertain. "
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    ABSTRACT: We investigated whether there is an association between increased risk for autism spectrum disorders (ASD) and selective serotonin reuptake inhibitors (SSRIs) used during pregnancy. This study used Denmark's health and population registers to obtain information regarding prescription drugs, ASD diagnosis, and health and socioeconomic status. There were 1.5 % of cases and 0.7 % of controls exposed to SSRIs during the pregnancy period, and higher effect estimates observed with longer use. We found evidence that in utero exposure to SSRIs increases a child's risk associated with ASD. These results, while adding to the limited knowledge on prenatal pharmacological exposures as potential ASD risk factors, need to be balanced against the benefits of indicated medication use by pregnant mothers.
    Journal of Autism and Developmental Disorders 05/2014; 44(10). DOI:10.1007/s10803-014-2128-4 · 3.06 Impact Factor
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