Skip to main content
SpringerLink
Log in

Genome-Wide Expression Studies in Autism-Spectrum Disorders: Moving from Neurodevelopment to Neuroimmunology

  • Chapter
  • First Online:
Genomics, Proteomics, and the Nervous System

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 2))

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington: American Psychiatric Press.

    Google Scholar 

  • Ashwood, P., Wills, S., & Van de Water, J. (2006). The immune response in autism: a new frontier for autism research. Journal of Leukocyte Biology, 80, 1–15.

    Article  PubMed  CAS  Google Scholar 

  • Baranzini, S. E., Bernard, C. C., & Oksenberg, J. R. (2005). Modular transcriptional activity characterizes the initiation and progression of autoimmune encephalomyelitis. Journal of Immunology, 174, 7412–7422.

    CAS  Google Scholar 

  • Bauman, M. L., & Kemper, T. L. (2005). Neuroanatomic observations of the brain in autism: a review and future directions. International Journal of Developmental Neuroscience, 23, 183–187.

    Article  PubMed  Google Scholar 

  • Boulanger, L. M. (2004). MHC class I in activity-dependent structural and functional plasticity. Neuron Glia Biology, 1, 283–289.

    Article  PubMed  Google Scholar 

  • Braunschweig, D., Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Croen, L. A., et al. (2008). Autism: maternally derived antibodies specific for fetal brain proteins. Neurotoxicology, 29, 226–231.

    PubMed  CAS  Google Scholar 

  • Cabanlit, M., Wills, S., Goines, P., Ashwood, P., & Van de Water, J. (2007). Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder. Annals of the New York Academy of Sciences, 1107, 92–103.

    Article  PubMed  CAS  Google Scholar 

  • Campbell, D. B., Buie, T. M., Winter, H., Bauman, M., Sutcliffe, J. S., Perrin, J. M., et al. (2009). Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions. Pediatrics, 123, 1018–1024.

    Article  PubMed  Google Scholar 

  • Chez, M. G., Dowling, T., Patel, P. B., Khanna, P., & Kominsky, M. (2007). Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatric Neurology, 36, 361–365.

    Article  PubMed  Google Scholar 

  • Cohly, H. H., & Panja, A. (2005). Immunological findings in autism. International Review of Neurobiology, 71, 317–341.

    Article  PubMed  CAS  Google Scholar 

  • Comi, A. M., Zimmermann, A. W., Frye, V. H., Law, P. A., & Peeden, J. N. (1999). Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. Journal of Autism and Developmental Disorders, 35, 103–116.

    Google Scholar 

  • Connolly, A. M., Chez, M., Streif, E. M., Keeling, R. M., Golumbek, P. T., Kwon, J. M., et al. (2006). Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy. Biological Psychiatry, 59, 354–363.

    Article  PubMed  CAS  Google Scholar 

  • Courchesne, E., Pierce, K., Schumann, C. M., Redcay, E., Buckwalter, J. A., Kennedy, D. P., et al. (2007). Mapping early brain development in autism. Neuron, 56, 399–413.

    Article  PubMed  CAS  Google Scholar 

  • Croen, L. A., Braunschweig, D., Haapanen, L., Yoshida, C. K., Fireman, B., Grether, J. K., et al. (2008). Maternal mid-pregnancy autoantibodies to fetal brain protein: the early markers for autism study. Biological Psychiatry, 64, 583–588.

    Article  PubMed  CAS  Google Scholar 

  • Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Van de Water, J. (2005). Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrumdisorders: a case-control study. Archives of Pediatrics & Adolescent Medicine, 159, 151–157.

    Article  Google Scholar 

  • Croonenberghs, J., Bosmans, E., Deboutte, D., Kenis, G., & Maes, M. (2002). Activation of the inflammatory response system in autism. Neuropsychobiology, 45, 1–6.

    Article  PubMed  CAS  Google Scholar 

  • Curran, L. K., Newschaffer, C. J., Lee, L. C., Crawford, S. O., Johnston, M. V., & Zimmerman, A. W. (2007). Behaviors associated with fever in children with autism spectrum disorders. Pediatrics, 120, e1386–e1392.

    Article  PubMed  Google Scholar 

  • D’Eufemia, P., Celli, M., Finocchiaro, R., Pacifico, L., Viozzi, L., Zaccagnini, M., et al. (1996). Abnormal intestinal permeability in children with autism. Acta Paediatrica, 85, 1076–1079.

    Article  PubMed  Google Scholar 

  • Dalton, P., Deacon, R., Blamire, A., Pike, M., McKinlay, I., Stein, J., et al. (2003). Maternal neuronal antibodies associated with autism and a language disorder. Annals of Neurology, 53, 533–537.

    Article  PubMed  Google Scholar 

  • DiCicco-Bloom, E., Lord, C., Zwaigenbaum, L., Courchesne, E., Dager, S. R., Schmitz, C., et al. (2006). The developmental neurobiology of autism spectrum disorder. The Journal of Neuroscience, 26, 6897–6906.

    Article  PubMed  CAS  Google Scholar 

  • Du, X., Tang, Y., Xu, H., Lit, L., Walker, W., Ashwood, P., et al. (2006). Genomic profiles for human peripheral blood T cells, B cells, natural killer cells, monocytes, and polymorphonuclear cells: comparisons to ischemic stroke, migraine, and Tourette syndrome. Genomics, 87, 693–703.

    Article  PubMed  CAS  Google Scholar 

  • Engstrom, A. H., Ohlson, S., Stubbs, E. G., Maciulus, A., Caldwell, V., Odell, J. D., et al. (2003). Decreased expression of CD95 (FAS/APO-1) on CD4+ T-lymphocytes from participants with autism. Journal of Developmental and Physical Disabilities, 15, 155–163.

    Article  Google Scholar 

  • Enstrom, A., Krakowiak, P., Onore, C., Pessah, I. N., Hertz-Picciotto, I., Hansen, R. L., et al. (2009a). Increased IgG4 levels in children with autism disorder. Brain, Behavior, and Immunity, 23, 389–395.

    Article  PubMed  CAS  Google Scholar 

  • Enstrom, A., Lit, L., Onore, C. E., Gregg, J. P., Hansen, R. L., Pessah, I. N., et al. (2009b). Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain, Behavior, and Immunity, 23, 124–133.

    Article  PubMed  CAS  Google Scholar 

  • Eto, I., Bandy, M. D., & Butterworth, C. E., Jr. (1992). Plasma and urinary levels of biopterin, neopterin, and related pterins and plasma levels of folate in infantile autism. Journal of Autism and Developmental Disorders, 22, 295–308.

    Article  PubMed  CAS  Google Scholar 

  • Fatemi, S. H., Earle, J., Kanodia, R., Kist, D., Emamian, E. S., Patterson, P. H., et al. (2002). Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia. Cellular and Molecular Neurobiology, 22, 25–33.

    Article  PubMed  Google Scholar 

  • Ferrante, P., Saresella, M., Guerini, F. R., Marzorati, M., Musetti, M. C., & Cazzullo, A. G. (2003). Significant association of HLA A2-DR11 with CD4 naive decrease in autistic children. Biomedicine & Pharmacotherapy, 57, 372–374.

    Article  CAS  Google Scholar 

  • Fombonne, E. (1999). The epidemiology of autism: a review. Psychological Medicine, 29, 769–786.

    Article  PubMed  CAS  Google Scholar 

  • Garbett, K., Ebert, P. J., Mitchell, A., Lintas, C., Manzi, B., Mirnics, K., et al. (2008). Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiology of Disease, 30, 303–311.

    Article  PubMed  CAS  Google Scholar 

  • Gershwin, M. E., Haselwood, D., Dorshkind, K., & Castles, J. J. (1979). Altered responsiveness to mitogens in subgroups of patients with juvenile rheumatoid arthritis. Journal of Clinical & Laboratory Immunology, 1, 293–297.

    CAS  Google Scholar 

  • Gregg, J. P., Lit, L., Baron, C. A., Hertz-Picciotto, I., Walker, W., Davis, R. A., et al. (2008). Gene expression changes in children with autism. Genomics, 91, 22–29.

    Article  PubMed  CAS  Google Scholar 

  • Heuer, L., Ashwood, P., Schauer, J., Goines, P., Krakowiak, P., Hertz-Picciotto, I., et al. (2008). Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Research, 1, 275–283.

    Article  PubMed  Google Scholar 

  • Holterhus, P. M., Hiort, O., Demeter, J., Brown, P. O., & Brooks, J. D. (2003). Differential gene-expression patterns in genital fibroblasts of normal males and 46, XY females with androgen insensitivity syndrome; evidence for early programming involving the androgen receptor. Genome Biology, 4, R37.

    Article  PubMed  Google Scholar 

  • Hornig, M., Solbrig, M., Horscroft, N., Weissenböck, H., & Lipkin, W. I. (2001). Borna disease virus infection of adult and neonatal rats: models for neuropsychiatric disease. Current Topics in Microbiology and Immunology, 253, 157–177.

    PubMed  CAS  Google Scholar 

  • Hu, V. W., Frank, B. C., Heine, S., Lee, N. H., & Quackenbush, J. (2006). Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes. BMC Genomics, 7, 118.

    Article  PubMed  Google Scholar 

  • Hu, V. W., Sarachana, T., Kim, K. S., Nguyen, A., Kulkarni, S., Steinberg, M. E., et al. (2009). Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism. Autism Research, 2(2), 78–97.

    Article  PubMed  Google Scholar 

  • Huh, G. S., Boulanger, L. M., Du, H., Riquelme, P. A., Brotz, T. M., & Shatz, C. J. (2000). Functional requirement for class I MHC in CNS development and plasticity. Science, 290, 2155–2159.

    Article  PubMed  CAS  Google Scholar 

  • Iglesias, A. H., Camelo, S., Hwang, D., Villanueva, R., Stephanopoulos, G., & Dangond, F. (2004). Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells. Journal of Neuroimmunology, 150, 163–177.

    Article  PubMed  CAS  Google Scholar 

  • Jyonouchi, H., Geng, L., Ruby, A., & Zimmerman-Bier, B. (2005). Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention. Neuropsychobiology, 51, 77–85.

    Article  PubMed  Google Scholar 

  • Jyonouchi, H., Sun, S., & Le, H. (2001). Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. Journal of Neuroimmunology, 120, 170–179.

    Article  PubMed  CAS  Google Scholar 

  • Kakiuchi, C., Iwamoto, K., Ishiwata, M., Bundo, M., Kasahara, T., Kusumi, I., et al. (2003). Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Nature Genetics, 35, 171–175.

    Article  PubMed  CAS  Google Scholar 

  • Korvatska, E., Van de Water, J., Anders, T. F., & Gershwin, M. E. (2002). Genetic and immunologic considerations in autism. Neurobiology of Disease, 9, 107–125.

    Article  PubMed  CAS  Google Scholar 

  • Lainhart, J. E., Bigler, E. D., Bocian, M., Coon, H., Dinh, E., Dawson, G., et al. (2006). Head circumference and height in autism: a study by the collaborative program of excellence in autism. American Journal of Medical Genetics, 140, 2257–2274.

    PubMed  Google Scholar 

  • Li, X., Chauhan, A., Sheikh, A. M., Patil, S., Chauhan, V., Li, X. M., et al. (2009). Elevated immune response in the brain of autistic patients. Journal of Neuroimmunology, 207, 111–116.

    Article  PubMed  CAS  Google Scholar 

  • Lintas, C., & Persico, A. M. (2009). Autistic phenotypes and genetic testing: state-of-the-art for the clinical geneticist. Journal of Medical Genetics, 46, 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Lintas, C., Sacco, R., Garbett, K., Mirnics, K., Militerni, R., Bravaccio, C., et al. (2009). Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression. Molecular Psychiatry, 14(7), 705–718.

    Article  PubMed  CAS  Google Scholar 

  • Martin, L. A., Ashwood, P., Braunschweig, D., Cabanlit, M., Van de Water, J., & Amaral, D. G. (2008). Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain, Behavior, and Immunity, 22, 806–816.

    Article  PubMed  CAS  Google Scholar 

  • Messahel, S., Pheasant, A. E., Pall, H., Ahmed-Choudhury, J., Sungum-Paliwal, R. S., & Vostanis, P. (1998). Urinary levels of neopterin and biopterin in autism. Neuroscience Letters, 241, 17–20.

    Article  PubMed  CAS  Google Scholar 

  • Meyer, U., Nyffeler, M., Engler, A., Urwyler, A., Schedlowski, M., Knuesel, I., et al. (2006). The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. The Journal of Neuroscience, 26, 4752–4762.

    Article  PubMed  CAS  Google Scholar 

  • Miller, M. T., Stromland, K., Ventura, L., Johansson, M., Bandim, J. M., & Gillberg, C. (2005). Autism associated with conditions characterized by developmental errors in early embryogenesis: a mini review. International Journal of Developmental Neuroscience, 23, 201–219.

    Article  PubMed  Google Scholar 

  • Molloy, C. A., Morrow, A. L., Meinzen-Derr, J., Schleifer, K., Dienger, K., Manning-Courtney, P., et al. (2006). Elevated cytokine levels in children with autism spectrum disorder. Journal of Neuroimmunology, 172, 198–205.

    Article  PubMed  CAS  Google Scholar 

  • Mouridsen, S. E., Rich, B., Isager, T., & Nedergaard, N. J. (2007). Autoimmune diseases in parents of children with infantile autism: a case-control study. Developmental Medicine and Child Neurology, 49, 429–432.

    Article  PubMed  Google Scholar 

  • Nishimura, Y., Martin, C. L., Vazquez-Lopez, A., Spence, S. J., Alvarez-Retuerto, A. I., Sigman, M., et al. (2007). Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways. Human Molecular Genetics, 16, 1682–1698.

    Article  PubMed  CAS  Google Scholar 

  • Odell, D., Maciulis, A., Cutler, A., Warren, L., McMahon, W. M., Coon, H., et al. (2005). Confirmation of the association of the C4B null allelle in autism. Human Immunology, 66, 140–145.

    Article  PubMed  CAS  Google Scholar 

  • Pardo, C. A., Vargas, D. L., & Zimmerman, A. W. (2005). Immunity, neuroglia and neuroinflammation in autism. International Review of Psychiatry, 17, 485–495.

    Article  PubMed  Google Scholar 

  • Patterson, P. H. (2002). Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness. Current Opinion in Neurobiology, 12, 115–118.

    Article  PubMed  CAS  Google Scholar 

  • Patterson, P. H. (2009). Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behavioural Brain Research, 204(2), 313–321.

    Article  PubMed  CAS  Google Scholar 

  • Persico, A. M., & Bourgeron, T. (2006). Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends in Neurosciences, 29, 349–358.

    Article  PubMed  CAS  Google Scholar 

  • Piven, J., Palmer, P., Jacobi, D., Childress, D., & Arndt, S. (1997). Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. The American Journal of Psychiatry, 154, 185–190.

    PubMed  CAS  Google Scholar 

  • Plioplys, A. V., Greaves, A., Kazemi, K., & Silverman, E. (1994). Lymphocyte function in autism and Rett syndrome. Neuropsychobiology, 29, 12–16.

    Article  PubMed  CAS  Google Scholar 

  • Ponzio, N. M., Servatius, R., Beck, K., Marzouk, A., & Kreider, T. (2007). Cytokine levels during pregnancy influence immunological profiles and neurobehavioral patterns of the offspring. Annals of the New York Academy of Sciences, 1107, 118–128.

    Article  PubMed  CAS  Google Scholar 

  • Purcell, A. E., Jeon, O. H., Zimmerman, A. W., Blue, M. E., & Pevsner, J. (2001). Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology, 57, 1618–1628.

    Article  PubMed  CAS  Google Scholar 

  • Reichelt, W. H., Knivsberg, A. M., Nodland, M., Stensrud, M., & Reichelt, K. L. (1997). Urinary peptide levels and patterns in autistic children from seven countries, and the effect of dietary intervention after 4 years. Developemental Brain Dysfunctions, 10, 44–55.

    Google Scholar 

  • Sacco, R., Militerni, R., Frolli, A., Bravaccio, C., Gritti, A., Elia, M., et al. (2007). Clinical, ­morphological, and biochemical correlates of head circumference in autism. Biological Psychiatry, 62, 1038–1047.

    Article  PubMed  CAS  Google Scholar 

  • Shi, L., Fatemi, S. H., Sidwell, R. W., & Patterson, P. H. (2003). Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. The Journal of Neuroscience, 23, 297–302.

    PubMed  Google Scholar 

  • Shi, L., Smith, S. E., Malkova, N., Tse, D., Su, Y., & Patterson, P. H. (2009). Activation of the maternal immune system alters cerebellar development in the offspring. Brain, Behavior, and Immunity, 23, 116–123.

    Article  PubMed  Google Scholar 

  • Singer, H. S., Morris, C. M., Gause, C. D., Gillin, P. K., Crawford, S., & Zimmermann, A. W. (2008). Antibodies against fetal brain in sera of mothers with autistic children. Journal of Neuroimmunology, 194, 165–172.

    Article  PubMed  CAS  Google Scholar 

  • Singh, V. K. (1996). Plasma increase of interleukin-12 and interferon-gamma. Pathological ­significance in autism. Journal of Neuroimmunology, 66, 143–145.

    Article  PubMed  CAS  Google Scholar 

  • Smith, S. E., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007). Maternal immune ­activation alters fetal brain development through interleukin-6. The Journal of Neuroscience, 27, 10695–10702.

    Article  PubMed  CAS  Google Scholar 

  • Sperner-Unterweger, B., Winkler, C., & Fuchs, D. (2006). Immune activation in autism. Pediatric Neurology, 34, 333.

    Article  PubMed  Google Scholar 

  • Sweeten, T. L., Posey, D. J., & McDougle, C. J. (2003). High blood monocyte counts and ­neopterin levels in children with autistic disorder. The American Journal of Psychiatry, 160, 1691–1693.

    Article  PubMed  Google Scholar 

  • Sweeten, T. L., Posey, D. J., Shankar, S., & McDougle, C. J. (2004). High nitric oxide production in autistic disorder: a possible role for interferon-gamma. Biological Psychiatry, 55, 434–437.

    Article  PubMed  CAS  Google Scholar 

  • Tang, Y., Schapiro, M. B., Franz, D. N., Patterson, B. J., Hickey, F. J., Schorry, E. K., et al. (2004). Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis type 1, and Down’s syndrome. Annals of Neurology, 56, 808–814.

    Article  PubMed  CAS  Google Scholar 

  • Tani, Y., Fernell, E., Watanabe, Y., Kanai, T., & Långström, B. (1994). Decrease in 6R–5, 6, 7, 8-tetrahydrobiopterin content in cerebrospinal fluid of autistic patients. Neuroscience Letters, 181, 169–172.

    Article  PubMed  CAS  Google Scholar 

  • Torres, A. R., Maciulis, A., & Odell, D. (2001). The association of MHC genes with autism. Frontiers in Bioscience, 6, D936–D943.

    Article  PubMed  CAS  Google Scholar 

  • Tuchman, R., & Rapin, I. (2002). Epilepsy in autism. Lancet Neurology, 1, 352–358.

    Article  PubMed  Google Scholar 

  • Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57, 67–81.

    Article  PubMed  CAS  Google Scholar 

  • Vervliet, G., & Schandene, L. (1985). In vitro correction of the interleukin-2 and interferon-gamma defect in multiple sclerosis. Clinical and Experimental Immunology, 61, 556–561.

    PubMed  CAS  Google Scholar 

  • Vojdani, A., Campbell, A. W., Anyanwu, E., Kashanian, A., Bock, K., & Vojdani, E. (2002). Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A. Journal of Neuroimmunology, 129, 168–177.

    Article  PubMed  CAS  Google Scholar 

  • Warren, R. P., Foster, A., & Margaretten, N. C. (1987). Reduced natural killer cell activity in autism. Journal of the American Academy of Child and Adolescent Psychiatry, 26, 333–335.

    Article  PubMed  CAS  Google Scholar 

  • Warren, R. P., Odell, J. D., Warren, W. L., Burger, R. A., Maciulis, A., Daniels, W. W., et al. (1996). Strong association of the third hypervariable region of HLA-DR beta 1 with autism. Journal of Neuroimmunology, 67, 97–102.

    Article  PubMed  CAS  Google Scholar 

  • Warren, R. P., Odell, J. D., Warren, W. L., Burger, R. A., Maciulis, A., Daniels, W. W., et al. (1997). Immunoglobulin A deficiency in a subset of autistic subjects. Journal of Autism and Developmental Disorders, 27, 187–192.

    Article  PubMed  CAS  Google Scholar 

  • Warren, R. P., Yonk, L. J., Burger, R. A., Cole, P., Odell, J. D., Warren, W. L., et al. (1990). Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in autism. Immunological ­investigations, 19, 245–251.

    Article  PubMed  CAS  Google Scholar 

  • Wills, S., Cabanlit, M., Bennett, J., Ashwood, P., Amaral, D. G., & Van de Water, J. (2009). Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders. Brain, Behavior, and Immunity, 23, 64–74.

    Article  PubMed  CAS  Google Scholar 

  • Wirleitner, B., Neurauter, G., Schröcksnadel, K., Frick, B., & Fuchs, D. (2003). Interferon-gamma-induced conversion of tryptophan: immunologic and neuropsychiatric aspects. Current Medicinal Chemistry, 10, 1581–1591.

    Article  PubMed  CAS  Google Scholar 

  • Yamashita, Y., Fujimoto, C., Nakajima, E., Isagai, T., & Matsuishi, T. (2003). Possible association between congenital cytomegalovirus infection and autistic disorder. Journal of Autism and Developmental Disorders, 33, 455–459.

    Article  PubMed  Google Scholar 

  • Zilbovicius, M., Meresse, I., Chabane, N., Brunelle, F., Samson, Y., & Boddaert, N. (2006). Autism, the superior temporal sulcus and social perception. Trends in Neurosciences, 29, 359–366.

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman, A. W., Connors, S. L., Matteson, K. J., Lee, L. C., Singer, H. S., Castaneda, J. C., et al. (2007). Maternal antibrain antibodies in autism. Brain, Behavior, and Immunity, 21, 351–357.

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman, A. W., Jyonouchi, H., Comi, A. M., Connors, S. L., Milstien, S., Varsou, A., et al. (2005). Cerebrospinal fluid and serum markers of inflammation in autism. Pediatric Neurology, 33, 195–201.

    Article  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Psychiatry and Neurogenetics, University “Campus Bio-Medico”, Via Alvaro del Portillo 21, 00128, Rome, Italy

    Antonio M. Persico

  2. Department of Psychiatry, Vanderbilt University, 8130A MRB III, 465 21st Avenue South, Nashville, TN, 37203, USA

    Károly Mirnics

Authors
  1. Roberto Sacco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio M. Persico
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Krassimira A. Garbett
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Károly Mirnics
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Antonio M. Persico or Károly Mirnics .

Editor information

Editors and Affiliations

  1. Nathan S. Kline Institute for, Psychiatric Research, New York University, Old Orangeburg Road 140, Orangeburg, 10962, New York, USA

    James D Clelland

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

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

Download citation

Publish with us

Policies and ethics

Search

Navigation