HLA-DR4 in Families With Autism

Lee, Li Ching; Leffell, Mary S.; Newschaffer, Craig J.; Matteson, Karla J.; Tyler, John D.; Zimmerman, Andrew W.

doi:10.1016/j.pediatrneurol.2006.06.006

Cited by 107 publications

(70 citation statements)

References 25 publications

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“…Moreover, familial auto-immune diseases were observed to be significantly more common in the ADHD group. The relationship among ADHD, a eurodevelopmental disease, and familial HLA-DR4 positivity was shown in previous studies (24,25). This association may explain the burden of familial auto immune diseases in the patient group.…”

Section: Discussionsupporting

confidence: 57%

Anti-Ganglioside, Anti-Glutamate, and Anti-Gad Antibody Levels in Attention-Deficit Hyperactivity Disorder

Özmen¹,

Demirci²,

Öztop³

et al. 2015

Erciyes Med J

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Objective: The etiology of Attention-Deficit Hyperactivite Disorder (ADHD) is still unclear. In the present study, we aimed to demonstrate the relationship among anti-ganglioside antibodies, anti-glutamate receptor antibodies, and anti-glutamic acit decarboksilaz (anti-GAD) antibodies, which are believed to be involved in the etiology of ADHD. Materials and Methods:The study included 36 children who were diagnosed with ADHD according to DSM IV diagnostic criteria and 21 healthy children as the control group. In all subjects, anti-ganglioside antibodies, anti-glutamate receptor antibodies, and anti-GAD antibodies were studied in the Microbiology Laboratory of Erciyes University, Medical School.Results: The mean age was 9.34 years in the ADHD group, which consisted of 5 girls and 31 boys. The mean age was 7.8 years in the control group, which consisted of 8 girls and 13 boys. No significant differences were observed in the levels of antiganglioside antibodies, anti-glutamate receptor antibodies, and anti-GAD antibodies between the ADHD and control groups. Conclusion:Although the etiology is unknown in ADHD, it is believed that autoimmune factors may be involved in the etiopathogenesis according to currently available information. However, there is a need for further studies with larger sample size to clarify the linkage between ADHD and anti-neuronal antibody levels.

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Section: Discussionsupporting

confidence: 57%

Anti-Ganglioside, Anti-Glutamate, and Anti-Gad Antibody Levels in Attention-Deficit Hyperactivity Disorder

Özmen¹,

Demirci²,

Öztop³

et al. 2015

Erciyes Med J

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“…This lack of specificity may suggest that the antibodies are generated as a consequence of some previous indiscriminate damage that involves different brain or CNS targets, leading to the generation of a diverse array of antibody specificities, as seen in ASD. Alternatively, the presence of these Lee et al 37 Differences were found between the geographical defined families and controls, but not between the geographical diverse families and controls. § Guerini et al 38 did not find an HLA linkage, but did find linkages to microsatellite regions in proximity to previously reported HLA linkages.…”

Section: Autoimmunity and Immune Dysfunction In Individuals With Asdmentioning

confidence: 96%

“…Further studies found that several HLA haplotypes, in particular HLA-DR4, occur more often in children with ASD than in the general population. 32,33,36,37 The HLA genes are located within a large genomic region referred to as the major histocompatibility complex (MHC). This region contains numerous other genes, including the complement protein C4 gene (C4A; alias C4B), which is important for innate immunity.…”

Section: Autoimmunity and Immune Dysfunction In Individuals With Asdmentioning

confidence: 99%

Immune Dysfunction in Autism: A Pathway to Treatment

2010

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Summary: Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Clinicians, schools, and service agencies worldwide have reported a dramatic increase in the number of children identified with autism. Despite expanding research, the etiology and underlying biological processes of autism remain poorly understood, and the relative contribution from genetic, epigenetic, and environmental factors remains unclear. Although autism affects primarily brain function (especially affect, social functioning, and cognition), it is unknown to what extent other organs and systems are disrupted. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment. A better understanding of the involvement of the immune response in autism, and of how early brain development is altered, may have important therapeutic implications.

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“…The DRB1*11 (Mostafa et al, 2013) and DRB1*1104 (Al-Hakbany et al, 2014) alleles have specifically been noted to occur at a higher rate in individuals with ASD. Multiple studies have suggested HLA-DR4 as another risk factor, appearing at increased rates in children with autism as well as their mothers (Johnson et al, 2009;Lee et al, 2006). Other positively associated alleles are the class I A*01, A*02, and B*07, while DRB1*03 and some DQB1 alleles have been negatively associated with rates of autism (Al-Hakbany et al, 2014;Mostafa et al, 2013;Torres et al, 2006).…”

Section: Immunogenetic Factorsmentioning

confidence: 99%

The Role of the Immune System in Autism Spectrum Disorder

Meltzer

Water

2016

Neuropsychopharmacol

405

293

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Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment.

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HLA-DR4 in Families With Autism

Cited by 107 publications

References 25 publications

Anti-Ganglioside, Anti-Glutamate, and Anti-Gad Antibody Levels in Attention-Deficit Hyperactivity Disorder

Anti-Ganglioside, Anti-Glutamate, and Anti-Gad Antibody Levels in Attention-Deficit Hyperactivity Disorder

Immune Dysfunction in Autism: A Pathway to Treatment

The Role of the Immune System in Autism Spectrum Disorder

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