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the major histocompatibility index, oxidative stress as well. 1: Altern Med Rev. 2002 Aug;7(4):292-316.Click here to read Links Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge base. * Kidd PM. Autism, archetype of the autistic spectrum disorders (ASD), is a neurodevelopmental disorder characterized by socially aloof behavior and impairment of language and social interaction. Its prevalence has surged in recent years. Advanced functional brain imaging has confirmed pervasive neurologic involvement. Parent involvement in autism management has accelerated understanding and treatment. Often accompanied by epilepsy, cognitive deficits, or other neurologic impairment, autism manifests in the first three years of life and persists into adulthood. Its etiopathology is poorly defined but likely multifactorial with heritability playing a major role. Prenatal toxic exposures (teratogens) are consistent with autism spectrum symptomatology. Frequent vaccinations with live virus and toxic mercurial content (thimerosal) are a plausible etiologic factor. Autistic children frequently have abnormalities of sulfoxidation and sulfation that compromise liver detoxification, which may contribute to the high body burden of xenobiotics frequently found. Frequent copper-zinc imbalance implies metallothionein impairment that could compound the negative impact of sulfur metabolism impairments on detoxification and on intestinal lining integrity. Intestinal hyperpermeability manifests in autistic children as dysbiosis, food intolerances, and exorphin (opioid) intoxication, most frequently from casein and gluten. Immune system abnormalities encompass derangement of antibody production, skewing of T cell subsets, aberrant cytokine profiles, and other impairments consistent with chronic inflammation and autoimmunity. Coagulation abnormalities have been reported. Part 2 of this review will attempt to consolidate progress in integrative management of autism, aimed at improving independence and lifespan for people with the disorder. PMID: 12197782
1: J Leukoc Biol. 2006 Jul;80(1):1-15. Epub 2006 May 12.Click here to read Links The immune response in autism: a new frontier for autism research.
* Ashwood P, * Wills S, * Van de Water J.
Medical Microbiology and Immunology and the M.I.N.D. Institute, University of California Davis, Sacramento, CA 95817, USA. pashwood@ucdavis.edu
Autism spectrum disorders (ASD) are part of a broad spectrum of neurodevelopmental disorders known as pervasive developmental disorders, which occur in childhood. They are characterized by impairments in social interaction, verbal and nonverbal communication and the presence of restricted and repetitive stereotyped behaviors. At the present time, the etiology of ASD is largely unknown, but genetic, environmental, immunological, and neurological factors are thought to play a role in the development of ASD. Recently, increasing research has focused on the connections between the immune system and the nervous system, including its possible role in the development of ASD. These neuroimmune interactions begin early during embryogenesis and persist throughout an individual's lifetime, with successful neurodevelopment contingent upon a normal balanced immune response. Immune aberrations consistent with a dysregulated immune response, which so far, have been reported in autistic children, include abnormal or skewed T helper cell type 1 (T(H)1)/T(H)2 cytokine profiles, decreased lymphocyte numbers, decreased T cell mitogen response, and the imbalance of serum immunoglobulin levels. In addition, autism has been linked with autoimmunity and an association with immune-based genes including human leukocyte antigen (HLA)-DRB1 and complement C4 alleles described. There is potential that such aberrant immune activity during vulnerable and critical periods of neurodevelopment could participate in the generation of neurological dysfunction characteristic of ASD. This review will examine the status of the research linking the immune response with ASD.
PMID: 16698940
1: Pathophysiology. 2006 Aug;13(3):171-81. Epub 2006 Jun 12.Click here to read Links Oxidative stress in autism.
* Chauhan A, * Chauhan V.
NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine (PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed.
PMID: 16766163
1: Hum Immunol. 2006 Apr-May;67(4-5):346-51. Epub 2006 Apr 3.Click here to read Links The association and linkage of the HLA-A2 class I allele with autism.
* Torres AR, * Sweeten TL, * Cutler A, * Bedke BJ, * Fillmore M, * Stubbs EG, * Odell D.
Center for Persons with Disabilities, Utah State University, Logan, UT 84322-6895, USA. rtorres@cpd2.usu.edu
Previous research has revealed associations between autism and immune genes located in the human leukocyte antigen (HLA). To better understand which HLA genetic loci may be associated with autism, we compared the class I HLA-A and -B alleles in autistic probands with case control subjects from Caucasian families. The frequency of HLA-A2 alleles was significantly increased in autistic subjects compared with normal allelic frequencies from the National Marrow Donors Program (NMDP) (p = 0.0043 after allelic correction). The transmission disequilibrium test for the A2 allele revealed an increased frequency of inheritance for autistic children (p = 0.033). There were no significant associations of autism with HLA-B alleles; however, the A2-B44 and A2-B51 haplotypes were two times more frequent in autistic subjects. The association and linkage of the class I HLA-A2 allele with autism suggests its involvement in the etiology of autism. Possible roles are discussed for the HLA-A2 association in the presentation of microbial antigen within the central nervous system and/or in the establishment of synaptic and neuronal circuits in the developing brain.
PMID: 16720216
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