Immunogenetic studies in autism and related disorders

Warren, Reed P.; Singh, Vijendra K.; Averett, R E; Odell, J. Dennis; Maciulis, Alma; Burger, Roger A.; Daniels, Wayne W.; Warren, W. Louise

doi:10.1007/bf02815207

Cited by 85 publications

(53 citation statements)

References 7 publications

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“…Autism and the immune system have been linked genetically and symptomatically (Warren et al, 1996;van Gent et al, 1997;Krause et al, 2002). Recent studies have shown that normal neurons in developing and adult brains express proteins of the major histocompatibility complex (MHC) class I, known for their role in the immune system (Corriveau et al, 1998;Huh et al, 2000).…”

Section: Linking Altered Structure and Function With Altered Neural Dmentioning

confidence: 99%

Autism and Abnormal Development of Brain Connectivity: Figure 1.

Belmonte¹,

Allen²,

et al. 2004

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It has been said that people with autism suffer from a lack of "central coherence," the cognitive ability to bind together a jumble of separate features into a single, coherent object or concept (Frith, 1989). Ironically, the same can be said of the field of autism research, which all too often seems a fragmented tapestry stitched from differing analytical threads and theoretical patterns. Defined and diagnosed by purely behavioral criteria, autism was first described and investigated using the tools of behavioral psychology. More recent years have added brain anatomy and physiology, genetics, and biochemistry, but results from these new domains have not been fully integrated with what is known about autistic behavior. The unification of these many levels of analysis will not only provide therapeutic targets for prevention and remediation of autism but can also provide a test case for theories of normal brain and cognitive development. Autism research therefore has much to learn from and much to offer to the broader neuroscience community. Clinical featuresClinically, autism is defined by a "triad" of deficits comprising impaired social interaction, impaired communication, restricted interests, and repetitive behaviors. Although in some cases speech never develops fully or never develops at all, in other cases, speech may be present but so inflexible and unresponsive to context that it is unusable in normally paced conversation; often, speech is limited to echolalia or confined to narrow topics of expertise in which discourse can proceed without conversational interplay. The communicative impairment extends also to nonverbal signals such as gaze, facial expression, and gesture. Social behaviors, too, are beset by a lack of flexibility and rapid coordination: children with autism do not coordinate attention between objects of mutual interest and the other people who may be interested in them, often engage in "parallel play" at the edge of a group rather than joining in cooperative play, and do not engage in pretend play. Intense and narrowly focused interests tend to concentrate on systems (Baron-Cohen, 2002) that operate deterministically and repeatably according to tractable sets of rules, whether these are abstract and complex systems such as computers or roleplaying games or very concrete and simple systems such as toilets or washing machines. Critical to identifying the causal factors of autism, and key to its relevance to normal development, is the recognition that autism is actually the extreme of a spectrum of abnormalities. Milder phenotypes on this spectrum include Asperger syndrome (Wing, 1981) in which language is relatively unimpaired, and the "Broader Autism Phenotype" in which characteristic cognitive traits are present subclinically . The combination of this broad variation of phenotypes and a 60 -90% concordance rate in identical twins suggests a large number of genetic and environmental biasing factors (Muhle et al., 2004). A basis in neural connectivity?In addition to the central coherence par...

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Section: Linking Altered Structure and Function With Altered Neural Dmentioning

confidence: 99%

Autism and Abnormal Development of Brain Connectivity: Figure 1.

Belmonte¹,

Allen²,

et al. 2004

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show abstract

“…18,19 Among the genes implicated in autism, several relate to immune regulation and function, including HLA-antigen presentation molecules and components of the complement system. 14,[20][21][22][23][24][25][26][27] Although abnormalities of cytokines and chemokines have been reported in the blood of patients with autism including plasma levels of tumor necrosis factor-a (TNF)-a, TNF receptor II, Interferon-gamma (IFNg), Interleukin-12 (IL-12), and IL-10, no definitive profile has emerged. Indeed, the changes reported in cytokine levels may occur in separate subgroups of autism subjects that have different clinical phenotypes.…”

Section: Introductionmentioning

confidence: 99%

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Corbett

Kantor²,

Schulman³

et al. 2006

Mol Psychiatry

167

113

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Modern methods that use systematic, quantitative and unbiased approaches are making it possible to discover proteins altered by a disease. To identify proteins that might be differentially expressed in autism, serum proteins from blood were subjected to trypsin digestion followed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF) instruments to identify differentially expressed peptides. Children with autism 4-6 years of age (n = 69) were compared to typically developing children (n = 35) with similar age and gender distributions. A total of 6348 peptide components were quantified. Of these, five peptide components corresponding to four known proteins had an effect size > 0.99 with a P < 0.05 and a Mascot identification score of 30 or greater for autism compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism. Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain. Despite limitations of the study, including the low fold changes and variable detection rates for the peptide components, the data support possible differences of circulating proteins in autism, and should help stimulate the continued search for causes and treatments of autism by examining peripheral blood.

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“…No genetic studies have been reported for prominent metalsusceptibility enzymes delta-aminolevulinic acid dehydratase (ALAD), coproporphyrinogen oxidase (CPOX), and stannin (SNN). Bias in histocompatibility haplotypes [29][30][31][32][33] may be indicative of exogenous infectious or inflammatory agents as contributory factors in autism.…”

Section: Genetic and Biochemical Markers In Asdmentioning

confidence: 99%

“…Gastrointestinal anomalies are frequent: in one study, 91% of ASD subjects were affected [128] . Inflammatory processes taking place in gut, compounded by immune system deficiencies [30,[129][130][131][132] may contribute to brain inflammation in ASD.…”

Section: Internal Sensingmentioning

confidence: 99%

Environmental Factors and Limbic Vulnerability in Childhood Autism

Lathe¹

2008

American J. of Biochemistry and Biotechnology

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Abstract:The rise in prevalence of autism spectrum disorders (ASD) is suggestive of a new etiology. Diagnostic substitution alone is unlikely to account for the increase, while genetic association with detoxification gene alleles points to an environmental contribution. Subtle structural anomalies in the ASD brain are widespread but limbic damage seems important for the development of behaviors diagnostic of ASD. The limbic brain is especially susceptible to environmental challenge: internal sensing, physiological feedback and neuroinflammatory processes may underlie this sensitivity to insult. Primary damage leading to ASD in later life is likely to take place in utero and/or in the immediate postnatal period. Despite evidence of heavy metal involvement, a causal connection may not yet be concluded because subjects exposed to metals tend to be exposed to other environmental agents. Because maternal minerals and lipids are supplied to the unborn child, historic toxic exposure of the mother may be pivotal. A two-hit combination of genetic susceptibility and environmental challenge is argued to underlie the rise in ASD.

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Immunogenetic studies in autism and related disorders

Cited by 85 publications

References 7 publications

Autism and Abnormal Development of Brain Connectivity: Figure 1.

Autism and Abnormal Development of Brain Connectivity: Figure 1.

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Environmental Factors and Limbic Vulnerability in Childhood Autism

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