European Journal of Pediatrics

, Volume 173, Issue 1, pp 33–43 | Cite as

Immune dysregulation in autism spectrum disorder

  • Daniela Briceno Noriega
  • Huub F. J. Savelkoul


Autism spectrum disorder (ASD) is a common and severe neuro-developmental disorder in early childhood which is defined by social and communication deficits and repetitive and stereotypic behaviours. The aetiology of ASD remains poorly understood. Susceptibility to development of ASD has significant environmental components, in addition to the profound genetic heritability. Few genes have been associated to the risk for ASD development. There is substantial evidence implicating chronic neurological inflammation and immune dysregulation leading to upregulation of inflammatory cytokines in the ASD brain, probably due to altered blood–brain barrier function. The immune system is characterized by excessive and skewed cytokine responses, modulated T cell reactivity, decreased regulation and production of immunosuppressive cytokines, modified NK function and increased autoantibody production. Conclusion: The perinatal environment generates vulnerability to chronic neuro-inflammation in the brain associated with profound modulation and dysregulation in the immune system leading to the rapid development of ASD in genetically susceptible children.


Autism Dietary intervention Immune mechanism Nutrition Inflammation Immunomodulation 


  1. 1.
    Abrahams BS, Geschwind DH (2008) Advances in autism spectrum disorder: on the threshold of a new neurobiology. Nat Rev Genet 9:341–355PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA (2011) Gastrointestinal flora and gastrointestinal status in children with autism—comparisons to typical children and correlation with autism severity. BMC Gastroenterol 11:22. doi:10.1186/1471-230X-11-22 PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Aghajafari F, Nagulesapilai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM (2013) Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. Br Med J 346:1136–1169CrossRefGoogle Scholar
  4. 4.
    American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
  5. 5.
    Ashwood P, Corbertt BA, Kantor A, Shulman H, Van de Water J, Amaral DG (2011) In search of cellular immunophenotype in blood of children with autism. PLoS One 6:19299CrossRefGoogle Scholar
  6. 6.
    Ashwood P, Enostrom A, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J (2008) Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behaviour outcomes. J Neuroimmunol 204:149–153PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Ashwood P, Wills S, van de Water J (2006) The immune response in autism: a new frontier for autism research. J Leukocyte Biol 80:1–15PubMedCrossRefGoogle Scholar
  8. 8.
    Atladottir HO, Henriksen TB, Schendel DE, Parner ET (2012) Autism after infection, febrile episodes and antibiotic use during pregnancy: an exploratory study. Pediatrics 130:1447–1454CrossRefGoogle Scholar
  9. 9.
    Atladottir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, Parner ET (2009) Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics 124:687–694PubMedCrossRefGoogle Scholar
  10. 10.
    Atladóttir HO, Thorsen P, Østergaard L, Schendel DE, Lemcke S, Abdallah M, Parner ET (2010) Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord 40:1423–1430PubMedCrossRefGoogle Scholar
  11. 11.
    Bolton PF, Dennis NR, Browne CE, Thomas NS, Veltman MW, Thompson RJ, Jacobs P (2002) The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders. Am J Med Genet 105:675–685CrossRefGoogle Scholar
  12. 12.
    Boyar FZ, Whitney MM, Lossie AC, Gray BA, Keller KL, Stalker HJ, Zori RT, Geffken G, Mutch J, Edge PJ, Voeller KS, Williams CA, Driscoll DJ (2001) A family with grand maternally derived interstitial duplication of proximal 15q. Clin Genet 60:421–230PubMedCrossRefGoogle Scholar
  13. 13.
    Braunschweig D, Ashwood P, Krakowiak P, Heetz-Picciotto I, Hansen R, Croen LA, Pessah IN, van de Water J (2008) Autism: maternally derived antibodies specific for fetal brain proteins. Neurotoxicology 29:226–231PubMedCentralPubMedGoogle Scholar
  14. 14.
    Braunschweig D, Duncanson P, Boyce R, Hansen R, Ashwood P, Pessah IN, Hertz-Picciotto I, Van de Water J (2012) Behavioral correlates of maternal antibody status among children with autism. J Autism Dev Disord 42:1435–1445PubMedCrossRefGoogle Scholar
  15. 15.
    Buie T, Campbell DB, Fuchs GJ, Futura GT, Levy J, van de Water J, Whitaker AH, Atkins, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinvo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Naotwocz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H (2010) Evaluation, diagnosis and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 125:S1–S18PubMedCrossRefGoogle Scholar
  16. 16.
    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. Ann N Y Acad Sci 1107:92–103PubMedCrossRefGoogle Scholar
  17. 17.
    Campbell DB, Buie TM, Winter H, Bauman M, Sutcliffe JS, Perrin JM, Levitt P (2009) Distinct genetic risk based on associations of MET in families with co-occurring autism and gastrointestinal conditions. Pediatrics 123:1018–1024PubMedCrossRefGoogle Scholar
  18. 18.
    Chakrabarti S, Fombonne E (2001) Pervasive developmental disorders in preschool children. JAMA 285:3093–3099PubMedCrossRefGoogle Scholar
  19. 19.
    Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN (1999) Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol 14:388–394PubMedCrossRefGoogle Scholar
  20. 20.
    Cornew L, Dobkins KR, Akshoomoff N, McCleery JP, Carver LJ (2012) Atypical social referencing in infant siblings of children with autism spectrum disorders. J Autism Dev Disord 42:2611–2621PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Courchense E, Carper R, Akshoomoff N (2003) Evidence of brain overgrowth in the first year of life in autism. JAMA 290:337–344CrossRefGoogle Scholar
  22. 22.
    Croen LA, Braunschweig D, Haapanen L, Yoshida CK, Fireman B, Grether JK, Kharazi M, Hansen RL, Ashwood P, Van de Water J (2008) Maternal mid-pregnancy autoantibodies to fetal brain protein: the early markers for autism study. Biol Psychiatry 64:583–588PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Curatolo P, Bombardieri R, Jozwiak S (2008) Tuberous sclerosis. Lancet 372:657–668PubMedCrossRefGoogle Scholar
  24. 24.
    Depino AM (2013) Peripheral and central inflammation in autism spectrum disorders. Mol Cell Neurosci 53:69–76PubMedCrossRefGoogle Scholar
  25. 25.
    Erickson CA, Stigler KA, Corkins MR, Posey DJ, Fitzgerald JF, McDougle CJ (2005) Gastrointestinal factors in autistic disorder: a critical review. J Autism Dev Dis 35:713–727CrossRefGoogle Scholar
  26. 26.
    Eyles DW, Burne TH, McGrath JJ (2013) Vitamin D: effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol 34:47–64PubMedCrossRefGoogle Scholar
  27. 27.
    Feron F, Burne TH, Brown J, Smith E, McGrath JJ, Mackay-Sim A, Eyles DW (2005) Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull 153:61–68Google Scholar
  28. 28.
    Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, Youn E, Summanen PH, Granpeesheh D, Dixon D, Liu M, Molitoris DR, Green JA (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16:444–453PubMedCrossRefGoogle Scholar
  29. 29.
    Folstein SE, Rosen-Sheidley B (2001) Genetics of autism: complex etiology for heterogeneous disorder. Nat Rev Genet 2:943–955PubMedCrossRefGoogle Scholar
  30. 30.
    Fombonne E (2002) Epidemiological trends in rates of autism. Mol Psychiatry 7:S4–S6PubMedCrossRefGoogle Scholar
  31. 31.
    Fombonne E (2003) Epidemiological surveys of autism and other pervasive developmental disorders: an update. J Autism Dev Disord 33:365–382PubMedCrossRefGoogle Scholar
  32. 32.
    Fox E, Amaral D, van de Water J (2012) Maternal and fetal antibrain antibodies in development and disease. Dev Neurobiol 72:1327–1334PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Gardener H, Spiegelman D, Buka SL (2009) Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry 195:7–14PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Geschwind DH (2009) Advances in autism. Annu Rev Med 60:367–380PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Gesundheit B, Rosenzweig JP, Naor D, Lerer B, Zachor DA, Prochazka V, Melamed M, Kristt DA, Steinberg A, Shulman C, Hwang P, Koren G, Walfisch A, Passweg JR, Snowden JA, Tamouza R, Lebover M, Farge-Bancel D, Ashwood P (2013) Immunological and autoimmune considerations of autism spectrum disorders. J Autoimmun 44:1–7. doi:10.1016/j.jaut.2013.05.005 PubMedCrossRefGoogle Scholar
  36. 36.
    Gilger MA, Redel CA (2009) Autism and the gut. Pediatrics 124:796–798PubMedCrossRefGoogle Scholar
  37. 37.
    Goines P, van de Water J (2010) The immune systems role in the biology of autism. Curr Opin Neurol 23:111–117PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Grigorenko EL, Han SS, Yrigollen CM, Leng L, Mizue Y, Anderson GM, Mulder EJ, de Bildt A, Minderaa MB, Volkmar FR, Chang JT, Bucala R (2008) Macrophage migration inhibitory factor and autism spectrum disorders. Pediatrics 122:438–445CrossRefGoogle Scholar
  39. 39.
    Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N (2011) Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 68:1095–1102PubMedCrossRefGoogle Scholar
  40. 40.
    Happe F, Ronald A (2008) The ‘fractionable autism triad’: a review evidence from behavioural, genetic, cognitive and neural research. Neuropsychol Rev 18:287–304PubMedCrossRefGoogle Scholar
  41. 41.
    Happe F, Ronald A, Plomin R (2006) Time to give up on a single explanation for autism. Nat Neurosci 9:1218–1220PubMedCrossRefGoogle Scholar
  42. 42.
    Heil KM, Schaaf C (2013) The genetics of autism spectrum disorders—a guide for clinicians. Curr Psychiatry Rep 15:334–343PubMedCrossRefGoogle Scholar
  43. 43.
    Herzing LB, Cook EH, Ledbetter DH (2002) Allele-specific expression analysis by RNA-FISH demonstrates preferential maternal expression of UBE3A and imprint maintenance within 15q11-q13 duplications. Hum Mol Genet 11:1707–1718PubMedCrossRefGoogle Scholar
  44. 44.
    Hewitson L (2013) Scientific challenges in developing biological markers for autism. OA Autism 1(1):7Google Scholar
  45. 45.
    Hochberg Z, Feil R, Constancia M, Fraga M, Junien C, Carel JC, Boileau P, Le Bouc Y, Deal CL, Lillycrop K, Scharfmann R, Sheppard A, Skinner M, Szyf M, Waterland RA, Waxman DJ, Whitelaw E, Ong K, Albertsson-Wikland K (2011) Child health, developmental plasticity, and epigenetic programming. Endocr Rev 32:159–224PubMedCrossRefGoogle Scholar
  46. 46.
    Hollander E, King A, Delaney K, Smith CJ, Silverman JM (2003) Obsessive compulsive behaviors in parents of multiplex autism families. Psychiatry Res 117:11–16PubMedCrossRefGoogle Scholar
  47. 47.
    Hutcheson HB, Olson LM, Bradford Y, Folstein SE, Santangelo SL, Sutcliffe JS, Haines JL (2004) Examination of NRCAM, LRRN3, KIAA0716 and LAMB1 as autism candidate genes. BMC Med Genet 5(12):1–14Google Scholar
  48. 48.
    Ibrahim SH, Voigt RG, Katusic AK, Weaver AL, Barbaresi WJ (2009) Incidence of gastrointestinal symptoms in children with autism in Olmsted County, Minnesota, 1976–1997: a population based study. Pediatrics 124:680–686PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    IMGSAC (2001) Further characterization of the autism susceptibility locus AUTS1 in chromosome 7q. Hum Mol Genet 10:973–982CrossRefGoogle Scholar
  50. 50.
    James WH (2012) A potential explanation of some established major risk factors for autism. Dev Med Child Neurol 54:301–305PubMedCrossRefGoogle Scholar
  51. 51.
    Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, Arden NK, Godfrey KM, Cooper C, Princess Anne Hospital Study Group (2006) Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet 367:36–43PubMedCrossRefGoogle Scholar
  52. 52.
    Johnson DD, Wagner CL, Husley TC, McNeil RB, Ebeling M, Hollis BW (2011) Vitamin D deficiency and insufficiency is common during pregnancy. Am J Perinat 28:007–012CrossRefGoogle Scholar
  53. 53.
    Johnson NL, Giarelli E, Lewis C, Rice CE (2012) Genomics and autism spectrum disorder. J Nurs Scholarsh 45:69–78CrossRefGoogle Scholar
  54. 54.
    Jyonouchi H, Geng L, Streck DL, Totuner A (2012) Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): a case study. J Neuroinflammation 9(4):1–12Google Scholar
  55. 55.
    Kemper TL, Bauman ML (2002) Neuropathology of infantile autism. Mol Psychiatry 7:12–13CrossRefGoogle Scholar
  56. 56.
    Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC, Cheon KA, Kim SJ, Kim YK, Lee H, Song DH, Grinker RR (2011) Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry 168:904–912PubMedGoogle Scholar
  57. 57.
    Kocovska E, Fernell E, Billstedt E, Minnis H, Gillberg C (2012) Vitamin D and autism: clinical review. Res Dev Disabil 33:1541–1550PubMedCrossRefGoogle Scholar
  58. 58.
    Korvatska E, van de Water J, Anders TF, Gershwin ME (2002) Genetic and immunologic considerations in autism. Neurobiol Dis 9:107–125PubMedCrossRefGoogle Scholar
  59. 59.
    Kumar RA, Christian SL (2009) Genetics of autism spectrum disorder. Curr Neurol Neurosci Rep 9:188–197PubMedCrossRefGoogle Scholar
  60. 60.
    Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, Ji L, Brown T, Malik M (2009) Elevated immune response in the brain of autistic patients. J Neuroimmunol 207:111–116PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Louis P (2012) Does the human gut microbiota contribute to the etiology of autism spectrum disorder? Dig Dis Sci 57:1987–1989PubMedCrossRefGoogle Scholar
  62. 62.
    Monnet-Tschudi F, Deafaux A, Braissant O, Cagnon L, Zurich MG (2011) Methods to assess neuroinflammation. Curr Protoc Toxicol. 11; Chapter 12: Unit 12.19. DOI: 10.1002/0471140856.tx1219s50
  63. 63.
    Morley R, Carlin JB, Pasco JA, Wark JD (2006) Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J Clin Endocrinol Meth 91:906–912CrossRefGoogle Scholar
  64. 64.
    Muhle R, Trentacoste SV, Rapin I (2004) The genetics of autism. Pediatrics 113:472–486CrossRefGoogle Scholar
  65. 65.
    Okada K, Hashimoto K, Iwata Y et al (2007) Decreased serum levels of transforming growth factor beta-1 in patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 31:187–190PubMedCrossRefGoogle Scholar
  66. 66.
    Olivié H (2012) Clinical practice. The medical care of children with autism. Eur J Pediatr 271:741–749CrossRefGoogle Scholar
  67. 67.
    Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, Bryson S, Carver LJ, Constantino JN, Dobkins K, Hutman T, Iverson JM, Landa R, Rogers SJ, Sigman M, Stone WL (2011) Recurrence risks for autism spectrum disorders: a baby siblings research consortium study. Pediatrics 128:e1. doi:10.1542/peds.2010-2825 CrossRefGoogle Scholar
  68. 68.
    Palmen SJ, van Engeland H, Hof PR, Schmitz C (2004) Neuropathological findings in autism. Brain 127:2572–2583PubMedCrossRefGoogle Scholar
  69. 69.
    Patterson P (2011) Maternal infection and immune involvement in autism. Trends Mol Med 17:389–394PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Ratacczak HV (2011) Theoretical aspects of autism: causes—a review. J Immunotoxicol 8:68–79CrossRefGoogle Scholar
  71. 71.
    Ricci S, Businaro R, Ippolliti F, Lo Vasco VR, Massoni F, Onofri E, Trolli GM, Pontecorvi V, Morelli M, Rapp Ricciardi M, Archer T (2013) Altered cytokine and BDNF levels in autism spectrum disorder. Neurotoxicol Res. doi:10.1007/s12640-013-9393-4 Google Scholar
  72. 72.
    Rosenberg RE, Law JK, Yenokyan G, McGready J, Kaufamann WE, Law PA (2009) Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Arch Pediatr Adolesc Med 163:907–914PubMedCrossRefGoogle Scholar
  73. 73.
    Sandhu B, Steer C, Golding J, Emond A (2009) The early stool patterns of young children with autistic spectrum disorder. Arch Dis Child 94:497–500PubMedCrossRefGoogle Scholar
  74. 74.
    Schaaf CP, Sabo A, Sakai Y, Crosby J, Muzny D, Hawes A, Lewis L, Akbar H, Varghese R, Boerwinkle E, Gibbs RA, Zoghbi HY (2011) Oligogenic heterozygosity in individuals with high functioning autism spectrum disorder. Hum Mol Genet 20:3366–3375PubMedCrossRefGoogle Scholar
  75. 75.
    Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HQ, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GAP, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJT, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi A, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Döhner H, Döhner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC (2003) Human chromosome 7: DNA sequence and biology. Science 300:767–772PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Shao Y, Wolpert CM, Raiford KL, Menold MM, Donnelly SL, Ravan SA, Bass MP, McClain C, von Wendt L, Vance JM, Abramson RH, Wright HH, Ashley-Koch A, Gilbert JL, DeLong RG, Cuccaro ML, Pericak-Vance MA (2002) Genomic screen and follow up analysis for autistic disorder. Am J Med Genet 69:327–340Google Scholar
  77. 77.
    Shattuck PT, Durkin M, Maenner M, Newschaffer C, Mandell DS, Wiggins L, Lee LC, Rice C, Giarelli E, Kirby R, Baio J, Pinto-Martin J, Cuniff C (2009) Timing of identification among children with an autism spectrum disorder: findings from a population-based surveillance study. J Am Acad Child Adolesc Psychiatry 48:474–483PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Shu W, Cho JY, Jiang Y, Zhang M, Weisz D, Elder GA, Schmeidler J, De Gasperi R, Sosa MA, Rabidou D, Santucci AC, Perl D, Morrisey E, Buxbaum JD (2005) Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. Proc Natl Acad Sci 102:9643–9648PubMedCrossRefGoogle Scholar
  79. 79.
    Siniscalo D, Bradstreet JJ, Antonucci N (2013) Therapeutic role of hematopoietic stem cells in autism spectrum disorder-related inflammation. Front Immunol 4:140. DOI 10.3389/fimmu.2013.00140 Google Scholar
  80. 80.
    Spiker D, Lotspeich LJ, Dimiceli, Szatmari P, Myers RM, Risch N (2001) Birth order defects on nonverbal IQ scores in autism multiplex families. J Autism Dev Disord 31:449–460PubMedCrossRefGoogle Scholar
  81. 81.
    Stevens MC, Feith DH, Waterhouse LH (2000) Season of birth effects in autism. J Clin Exp Neuropsychol 22:399–407PubMedCrossRefGoogle Scholar
  82. 82.
    Stewart C, Latif A (2008) Symptomatic nutritional rickets in a teenager with autistic spectrum disorder. Child Care Health Dev 34:276–278PubMedCrossRefGoogle Scholar
  83. 83.
    Steyaert JG, De La Marche W (2008) What's new in autism? Eur J Pediatr 167:1091–1101PubMedCrossRefGoogle Scholar
  84. 84.
    Sudarov A (2013) Defining the role of cerebellar Purkinje cells in autism spectrum disorders. Cerebellum 12:950–955. doi:10.1007/s12311-013-0490-y Google Scholar
  85. 85.
    Tchaconas A, Adesman A (2013) Autism spectrum disorder: a pediatric overview and update. Curr Opin Pediatr 25:130–144PubMedCrossRefGoogle Scholar
  86. 86.
    van Eeghen AM, Pulsifer MB, Merker VL, Neumeyer AM, van Eeghen EE, Thibert RL, Cole AJ, Leigh FA, Plotkin SR, Thiele EA (2013) Understanding relationships between autism, intelligence and epilepsy: a cross-disorder approach. Dev Med Child Neurol 55:146–153PubMedCrossRefGoogle Scholar
  87. 87.
    Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57:67–81Google Scholar
  88. 88.
    Vojdani A, Campbell AW, 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. J Neuroimmunol 129:168–177PubMedCrossRefGoogle Scholar
  89. 89.
    Walker SJ, Fortunato J, Gonzalez LG, Krigsman A (2013) Identification of unique gene expression profile in children with regressive autism spectrum disorder (ASD) and ileocolitis. PLoS ONE 8:e58058. doi:10.1371/journal.pone.0058058 PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Wang LV, Claus C, Sorich MJ, Gerber JP, Angley MT, Conion MA (2010) Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig Dis Sci 57:2096–2102CrossRefGoogle Scholar
  91. 91.
    Wassink TH, Hazlett HC, Epping EA, Arndt S, Dager SR, Schellenberg GD, Dawson G, Piven J (2007) Cerebral cortical gray matter overgrowth and functional variation of the serotonin transporter gene in autism. Arch Gen Psychiatry 64:709–717PubMedCrossRefGoogle Scholar
  92. 92.
    Werling DM, Geschwind DH (2013) Sex differences in autism spectrum disorder. Curr Opin Neurol 26:146–153PubMedCrossRefGoogle Scholar
  93. 93.
    Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Hart PH, Kusel MM (2012) Maternal vitamin D levels and the autism phenotype among offspring. J Autism Dev Disord 43:1495–1504CrossRefGoogle Scholar
  94. 94.
    Williams BL, Horning M, Buie T, Bauman ML, Cho Paik M, Wick I, Bennett JA, Jabado O, Hirschberg DL, Lipkin WI (2011) Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One 6:987–991CrossRefGoogle Scholar
  95. 95.
    Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, van de Water J (2007) Autoantibodies in autism spectrum disorders. Ann N Y Acad Sci 1107:79–91PubMedCrossRefGoogle Scholar
  96. 96.
    Wolpert CM, Menold MM, Bass MP, Qumsiyeh MB, Donnelly SL, Ravan SA, Vance JM, Gilbert JR, Abranson RK, Wright HH, Cuccaro ML, Pericak-Vance MA (2000) Three probands with autistic disorder and isodicentric chromosome 15. Am J Med Genet 96:365–372PubMedCrossRefGoogle Scholar
  97. 97.
    Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle C, Murphy C (2003) Prevalence of autism in a US metropolitan area. JAMA 289:49–55PubMedCrossRefGoogle Scholar
  98. 98.
    Zhang H, Dougherty PM (2011) Acute inhibition of signaling phenotype of spinal GABAergic neurons by tumor necrosis-alpha. J Physiol Lond 589:4511–4526PubMedGoogle Scholar
  99. 99.
    Ziats MN, Rennert OM (2013) Aberrant expression of long noncoding RNAs in autistic brain. J Mol Neurosci 49:589–593. doi:10.1007/s12031-012-9880-8 PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Zimmerman AW, Connors SL, Matteson KJ, Lee LC, Singer HS, Castaneda JA, Pearce DA (2007) Maternal antibrain antibodies in autism. Brain Behav Immun 21:351–357PubMedCrossRefGoogle Scholar
  101. 101.
    Zwaigenbaum L, Bryson SE, Szatmari P, Brian J, Smith IM, Roberts W, Vaillancourt T, Roncadin C (2012) Sex differences in children with autism spectrum disorder identified within a high risk infant cohort. J Autism Dev Disord 42:22585–22596CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Daniela Briceno Noriega
    • 1
  • Huub F. J. Savelkoul
    • 1
  1. 1.Cell Biology and Immunology GroupWageningen UniversityWageningenThe Netherlands

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