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Advanced Autism Thinking
Part 4

Genetic or infectious causes may cause some autistic children to have different results on protein and immune system tests.

For example, Amaral from UC Davis MIND Institute reported differences in the immune system cells. This and other research support the idea that the immune system plays an important role in autism.

Of the roughly 4,000 different proteins evaluated, the testing identified about 500 differences in proteins between the autistic and normally developing children. 100 protein differences were large. 1

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Autistic disorder and viral infections.

Libbey JE, Sweeten TL, McMahon WM, Fujinami RS.

Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism. [Bolding is mine]

J Neurovirol. 2005 Feb;11(1):1-10.

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Neuroglial activation and neuroinflammation in the brain of patients with autism.

Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA.

Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.

Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh-frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.

Ann Neurol. 2005 Jan;57(1):67-81.

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Plasma concentration of immunoglobulin classes and subclasses in children with autism in the Republic of Macedonia: retrospective study.

Trajkovski V, Ajdinski L, Spiroski M.

AIM: To examine plasma concentration of IgA, IgM, IgG classes, and IgG1, IgG2, IgG3, and IgG4 subclasses in children with autism. METHODS: Infantile autism was diagnosed by the Diagnostic and Statistical Manual for Mental Disorders (DSM)-IV and the International Classification of Diseases (ICD)-10 criteria. Plasma samples were collected from 35 autistic subjects, and their 21 siblings (biological brothers and sisters) who served as healthy controls. Plasma samples were separated by centrifugation and stored at -20 degrees C until the determination. Plasma immunoglobulin classes (IgM, IgA, IgG) and subclasses (IgG1, IgG2, IgG3, IgG4) were determined using a nephelometer. RESULTS: Plasma concentrations (mean+/-standard deviation) of IgM and IgG in autistic children (1.36+/-0.31 g/L and 13.14+/-1.27 g/L, respectively) were significantly higher (p=0.031 and p=0.023, respectively) in comparison with their healthy brothers or sisters (1.20+/-0.15 g/L and 12.39+/-0.96 g/L, respectively). Children with autism had significantly higher plasma concentrations of IgG4 (p<0.001) compared to their siblings (healthy brothers or sisters). Plasma concentration of IgA, IgG1, IgG2, and IgG3 were similar in autistic children and their healthy brothers or sisters. Increased plasma concentration of IgG1 was found (p=0.027) in autistic males (8.06+/-2.40), as compared with their healthy brothers (5.24+/-4.13 g/L). Plasma concentrations of IgG (14.28+/-3.66 g/L), and IgG1 (9.41+/-2.20 g/L) in autistic females were increased (p=0.012 and p=0.021, respectively) in comparison with IgG (11.07+/-2.07) and IgG1 (6.37+/-3.38 g/L) in their healthy sisters. CONCLUSION: Children with autism have increased plasma concentration of immunoglobulines. Increased immunoglobulines in children with autism could be a result of impaired development of the immune system, and/or genetic factors connected with defense mechanism in these children.

Croat Med J. 2004 Dec;45(6):746-9.

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Dr. J


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