Increased Frequency of the Extended or Ancestral Haplotype B44-SC3O-DR4 in Autism

Daniels, Wayne W.; Warren, Reed P.; Odell, J. Dennis; Maciulis, Alma; Burger, Roger A.; Warren, W. Louise; Torres, Anthony R.

doi:10.1159/000119223

Cited by 82 publications

(57 citation statements)

References 12 publications

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“…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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Section: Autoimmunity and Immune Dysfunction In Individuals With Asdmentioning

confidence: 99%

Immune Dysfunction in Autism: A Pathway to Treatment

2010

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“…In addition to genes related to specific neurotransmitter systems and to factors that directly regulate gene expression, recent studies have suggested that genes within the major histocompatibility complex (MHC, or HLA in humans), on chromosome 6p21.3, may encode predisposing factors in autism [253,78,252] (but see [197]). Genes in this region encode products that are required for self-nonself recognition by the adaptive immune system.…”

Section: Immunological Signallingmentioning

confidence: 99%

“…Genes in this region encode products that are required for self-nonself recognition by the adaptive immune system. In particular, an unusual number of people with autism may share all or part of the extended MHC haplotype B44-SC30-DR4 [253,78,252,232]. Evidence also exists for a link between autism and a null allele of the C4B gene, in the class III MHC region, [254], and correspondingly low levels of C4b protein [249] which is essential in activation of the classical complement pathway.…”

Section: Immunological Signallingmentioning

confidence: 99%

Autism as a disorder of neural information processing: directions for research and targets for therapy

et al. 2004

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“…A possible role of the HLA genes has also been proposed for other neurological disorders such as autism (5). Besides, it has been singled out that an HLA extended haplotype A2-B44-DR4 occurs with increased frequency in autism (9). The involvement of HLA-DR4 in autism spectrum disorder (ASD) has also been confirmed by the transmission disequilibrium test (TDT) that linked DR4 allele to ASD through the paternal chromosome (10).…”

Section: Discussionmentioning

confidence: 99%

Holly's Story: Illustration of an Attention Deficit Hyperactivity Disorder Case

Aureli

Piancatelli

Beato

et al. 2008

Int J Immunopathol Pharmacol

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During the last 10years a significant increase of childhood neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), has been reported. ADHD is believed to have a multifactorial etiology including multiple genetic and prenatal environmental factors. For this reason, there has been a recent revival regarding the role of autoimmunity in this pathology. An ADHD combined-type patient born from a drug-addicted mother was studied. Neuropsychological tests according to the criteria of the 4 th edition of the Diagnostic and Statistical Manual (DSM4) permitted us to make the ADHD-diagnosis. The HLA-A, -B, and -DRBI alleles of the child were determined by sequence-based typing (SBT) after DNA extraction. Although no autistic behavioral features were observed in the patient, a double genetic association between ADHD and autism was reported. In fact, HLA class I alleles (A*02 and B*44) associated to autism and the HLA class II allele (DRBI*04) associated both to autism and ADHD were identified.Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that arouses continuous and increasing interest from the clinicians and genetists oriented to individuate further details which will be able to help the affected children and their families. ADHD is a multifactorial illness often linked to other childhood disorders, and multiple genes of the immune system seem to be involved in its aetiopathogenesis (I). It is also very important to report the existence of non-genetic factors, such as a premature birth, maternal smoking during pregnancy, and prenatal drug exposure that may increase the risk for behavioral disorders (2). In this study, we investigate the genetic factors that could constitute the physiological bases of this neurobehavioral disorder. In particular, the HLA genes have been studied as a group of highly polymorphic genes, mainly responsible for autoimmune etiology of a large group of pathologies. MATERIALS AND METHODSHolly is the fictitious name of a nine-year old boy with an ADHD diagnosis who arrived at our institute with other pediatric patients who were admitted to a case-control study with the aim of finding a possible association between HLA region and childhood neuropsychiatric disorders. Holly is different from the other patients as he has a complex story and he presents a multiplicity of risk factors. Firstly, Holly's mother took drugs (heroin) during pregnancy. This fact elicited withdrawal symptoms

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Increased Frequency of the Extended or Ancestral Haplotype B44-SC3O-DR4 in Autism

Cited by 82 publications

References 12 publications

Immune Dysfunction in Autism: A Pathway to Treatment

Immune Dysfunction in Autism: A Pathway to Treatment

Autism as a disorder of neural information processing: directions for research and targets for therapy

Holly's Story: Illustration of an Attention Deficit Hyperactivity Disorder Case

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