Abstract
Autism has long been thought to stem from abnormal neurodevelopment. Surprisingly, microarray-based genome-wide expression studies, involving either postmortem brain tissue or lymphoblastoid cell lines, provide converging evidence supporting prominent roles for the immune system in the pathogenesis of autism-spectrum disorders (ASDs). In particular, bioinformatic analyses, employing biological databases and gene network prediction software, point toward the involvement of multiple genes interconnected in immune-related pathways. Taken together, these findings suggest that a dysreactive immune process could derange neurodevelopment during critical periods in a large subset of children with autism. These conclusions are also supported by neuropathological and immunological studies, which are briefly summarized. Genome-wide expression studies can thus lead to a better understanding of autism pathogenesis and facilitate the identification of subgroups of patients with a similar underlying pathophysiology (“endophenotypes”), eventually leading to more effective therapeutic strategies. The characterization of peripheral gene-expression patterns and immunological abnormalities can also contribute to design laboratory-based diagnostic tools for the early detection of ASDs.
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Acknowledgments
We would like to thank the donor families, the Autism Tissue Program (Princeton, N.J.), the Harvard Brain Tissue Resource Center (Belmont, MA), and the NICHD Brain and Tissue Bank (Baltimore, MD) for providing the brain tissue samples. A.M.P. is supported by the Italian Ministry for University, Scientific Research and Technology (PRIN n.2006058195), the Italian Ministry of Health (RFPS-2007-5-640174) and Autism Speaks (Princeton, NJ) and K.M. is supported by VUKC Startup Fund, R01 MH079299, and K02 MH070786.
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Sacco, R., Persico, A.M., Garbett, K.A., Mirnics, K. (2011). Genome-Wide Expression Studies in Autism-Spectrum Disorders: Moving from Neurodevelopment to Neuroimmunology. In: Clelland, J. (eds) Genomics, Proteomics, and the Nervous System. Advances in Neurobiology, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7197-5_18
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