Abstract Autism spectrum disorders (ASD) are a group of neuro-developmental disorders in early childhood which are defined by social difficulties, communication deficits and repetitive or restrictive interests and behaviours. The etiology of ASD remains poorly understood. Much research has shown that children with ASD suffer from immunological dysfunction. This article reviews the current research progress on immunological dysfunction in children with ASD, including abnormalities in immune cells, antibodies, complements, cytokines, major histocompatibility complex and their potential association with ASD, and explores the impacts of maternal immunological activation on the immune dysfunction of children with ASD.
WANG Tian-Tian,DU Lin,SHAN Ling et al. Research advances in immunological dysfunction in children with autism spectrum disorders[J]. CJCP, 2014, 16(12): 1289-1293.
WANG Tian-Tian,DU Lin,SHAN Ling et al. Research advances in immunological dysfunction in children with autism spectrum disorders[J]. CJCP, 2014, 16(12): 1289-1293.
Parellada M, Penzol MJ, Pina L, eT al. The neurobiology of auTism specTrum disorders[J]. Eur PsychiaTry, 2014, 29(1): 11-19.
[3]
Ashwood P, Krakowiak P, HerTz-PiccioTTo I, eT al. AlTered T cell responses in children wiTh auTism[J]. Brain Behav Immun, 2011, 25(5): 840-849.
[4]
Ashwood P, Wakefield AJ. Immune acTivaTion of peripheral blood and mucosal CD3+ lymphocyTe cyTokine profiles in children wiTh auTism and gasTroinTesTinal sympToms[J]. J Neuroimmunol, 2006,173(1-2): 126-134.
[5]
Ashwood P, AnThony A, TorrenTe F, eT al. SponTaneous mucosal lymphocyTe cyTokine profiles in children wiTh auTism and gasTroinTesTinal sympToms: mucosal immune acTivaTion and reduced counTer regulaTory inTerleukin-10[J]. J Clin Immunol, 2004, 24(6): 664-673.
Onore C, Careaga M, Ashwood P. The role of immune dysfuncTion in The paThophysiology of auTism[J]. Brain Behav Immun, 2012, 26(3): 383-392.
[8]
Ziv Y, SchwarTz M. Immune-based regulaTion of adulT neurogenesis: implicaTions for learning and memory[J]. Brain Behav Immun, 2008, 22(2): 167-176.
[9]
Ziv Y, Ron N, BuTovsky O, eT al. Immune cells conTribuTe To The mainTenance of neurogenesis and spaTial learning abiliTies in adulThood[J]. NaT Neurosci, 2006, 9(2): 268-275.
[10]
Ashwood P, CorbeTT BA, KanTor A, eT al. In search of cellular immunophenoTypes in The blood of children wiTh auTism[J]. PLoS One, 2011, 6(5): e19299.
[11]
Heuer LS, Rose M, Ashwood P, eT al. Decreased levels of ToTal immunoglobulin in children wiTh auTism are noT a resulT of B cell dysfuncTion[J]. J Neuroimmunol, 2012, 251(1-2): 94-102.
Vojdani A, Mumper E, Granpeesheh D, eT al. Low naTural killer cell cyToToxic acTiviTy in auTism: The role of gluTaThione, IL-2 and IL-15[J]. J Neuroimmunol, 2008, 205(1-2): 148-154.
[14]
EnsTrom AM, LiT L, Onore CE, eT al. AlTered gene expression and funcTion of peripheral blood naTural killer cells in children wiTh auTism[J]. Brain Behav Immun, 2009, 23(1): 124-133.
[15]
Shavelle RM, STrauss DJ, PickeTT J. Causes of deaTh in auTism[J]. J AuTism Dev Disord, 2001, 31(6): 569-576.
[16]
Goyal K, Miyan JA. Neuro-immune abnormaliTies in auTism and Their relaTionship wiTh The environmenT :a variable insulT model for auTism[J]. FronT Endocrinol(Lausanne), 2014, 5: 29.
[17]
SweeTen TL, Posey DJ, McDougle CJ. High blood monocyTe counTs and neopTerin levels in children wiTh auTisTic disorder[J]. Am J PsychiaTry, 2003, 160(9): 1691-1693.
[18]
Vargas DL, Nascimbene C, Krishnan C, eT al. Neuroglial ac-TivaTion and neuroinflammaTion in The brain of paTienTs wiTh auTism[J]. Ann Neurol, 2005, 57(1): 67-81.
[19]
Voineagu I, Wang X, JohnsTon P, eT al. TranscripTomic analysis of auTisTic brain reveals convergenT molecular paThology[J]. NaTure, 2011, 474(7351): 380-384.
[20]
Breece E, PacioTTi B, Nordahl CW, eT al. Myeloid dendriTic cells frequencies are increased in children wiTh auTism specTrum disorder and associaTed wiTh amygdala volume and repeTiTive behaviors[J]. Brain Behav Immun, 2013, 31: 69-75.
[21]
Ashwood P, Krakowiak P, HerTz-PiccioTTo I, eT al. ElevaTed plasma cyTokines in auTism specTrum disorders provide evidence of immune dys-funcTion and are associaTed wiTh impaired behavioral ouTcome[J]. Brain Behav Immun, 2011, 25(1): 40-45.
[22]
EnsTrom AM, Onore CE, Van de WaTer JA, eT al. DifferenTial monocyTe responses To TLR ligands in children wiTh auTism specTrum disorders[J]. Brain Behav Immun, 2010, 24(1): 64-71.
[23]
de la Mano A, GaTo A, Alonso MI, eT al. Role of inTerleukin-1beTa in The conTrol of neuroepiThelial proliferaTion and differenTiaTion of The spinal cord during developmenT[J]. CyTokine, 2007, 37(2): 128-137.
[24]
Handley MT, Lian LY, Haynes LP, eT al. STrucTural and funcTional deficiTs in a neuronal calcium sensor-1 muTanT idenTified in a case of auTisTic specTrum disor-der[J]. PLoS One, 2010, 5(5): e10534.
[25]
Goines PE, Ashwood P. CyTokine dysregulaTion in auTism specTrum disorders (ASD): possible role of The environmenT[J]. NeuroToxicol TeraTol, 2013, 36: 67-81.
[26]
Wei H, Zou H, Sheikh AM, eT al. IL-6 is increased in The cerebellum of auTisTic brain and alTers neural cell adhesion, migraTion and synapTic formaTion[J]. J NeuroinflammaTion, 2011, 8: 52.
[27]
Hsiao EY, PaTTerson PH. AcTivaTion of The maTernal immune sysTem induces endocrine changes in The placenTa via IL-6[J]. Brain Behav Immun, 2011, 25(4): 604-615.
[28]
Samuelsson AM, Jennische E, Hansson HA, eT al. PrenaTal exposure To inTerleu-kin-6 resulTs in inflammaTory neurodegeneraTion in hippocampus wiTh NMDA/GABA(A) dysregulaTion and impaired spaTial learning[J]. Am J Physiol Regul InTegr Comp Physiol, 2006, 290(5): R1345-R1356.
[29]
Okada K, HashimoTo K, IwaTa Y, eT al. Decreased serum levels of Transforming growTh facTor-beTa1 in paTienTs wiTh auTism[J]. Prog Neuropsychopharmacol Biol PsychiaTry, 2007, 31(1): 187-190.
[30]
Heupel K, Sargsyan V, Plomp JJ, eT al. Loss of Transforming growTh facTor-beTa 2 leads To impairmenT of cenTral synapse func-Tion[J]. Neural Dev, 2008, 3: 25.
[31]
Vashlishan AB, Madison JM, Dybbs M, eT al. An RNAi screen idenTifies genes ThaT regulaTe GABA synapses[J]. Neuron, 2008, 58(3): 346-361.
[32]
Goines PE, Croen LA, Braunschweig D, eT al. Increased midgesTaTional IFN-gamma, IL-4 and IL-5 in women bearing a child wiTh auTism: a case-conTrol sTudy[J]. Mol AuTism, 2011, 2: 13.
[33]
Abdallah MW, Larsen N, Grove J, eT al. AmnioTic fluid inflammaTory cyTokines: poTenTial markers of immunologic dysfuncTion in auTism specTrum disorders[J]. World J Biol PsychiaTry, 2013, 14(7): 528-538.
[34]
VicTorio SC, HavTon LA, Oliveira AL. Absence of IFNgamma expression induces neuronal degeneraTion in The spinal cord of adulT mice[J]. J NeuroinflammaTion, 2010, 7: 77.
[35]
Li X, Chauhan A, Sheikh AM, eT al. ElevaTed immune response in The brain of auTisTic paTienTs[J]. J Neuroimmunol, 2009, 207(1-2): 111-116.
[36]
EnsTrom A, Krakowiak P, Onore C, eT al. Increased IgG4 levels in children wiTh auTism disorder[J]. Brain Behav Immun, 2009, 23(3): 389-395.
[37]
Heuer L, Ashwood P, Schauer J, eT al. Reduced levels of immunoglobulin in children wiTh auTism correlaTes wiTh behavioral sympToms[J]. AuTism Res, 2008, 1(5): 275-283.
[38]
Wasilewska J, Kaczmarski M, STasiak-BarmuTa A, eT al. Low serum IgA and increased expression of CD23 on B lymphocyTes in peripheral blood in children wiTh regressive auTism aged 3-6 years old[J]. Arch Med Sci, 2012, 8(2): 324-331.
[39]
MosTafa GA, KiTchener N. Serum anTi-nuclear anTibodies as a marker of auToimmuniTy in EgypTian auTisTic children[J]. PediaTr Neurol, 2009, 40(2): 107-112.
[40]
Al-Ayadlhi LY, MosTafa GA. Increased serum levels of anTi-ganglioside M1 auTo-anTibodies in auTisTic children: relaTion To The disease severiTy[J]. J NeuroinflammaTion, 2011, 8: 39.
[41]
Al-ayadhi LY, MosTafa GA. Increased serum osTeoponTin levels in auTisTic children: relaTion To The disease severiTy[J]. Brain Behav Immun, 2011, 25(7): 1393-1398.
[42]
Al-Ayadlhi LY, MosTafa GA. A lack of associaTion beTween hyperseroTonemia and The increased frequency of serum anTi-myelin basic proTein auTo-anTibodies in auTisTic children[J]. J NeuroinflammaTion, 2011, 8: 71.
[43]
Al-Ayadlhi LY, MosTafa GA. Serum anTinucleosome-specific anTibody as a maker of auToimmuniTy in children wiTh auTism[J]. J NeuroinflammaTion, 2014, 11: 69.
[44]
CorbeTT BA, KanTor AB, Schulman H, eT al. A proTeomic sTudy of serum from children wiTh auTism showing differenTial expression of apolipoproTeins and complemenT proTeins[J]. Mol PsychiaTry, 2007, 12(3): 292-306.
[45]
Odell D, Maciulis A, CuTler A, eT al. ConfirmaTion of The associaTion of C4B null allele in auTism[J].Human Immonol, 2005, 66(2): 140-145.
[46]
Al-Hakbany M, Awadallah S, Al-Ayadhi L. The relaTionship of HLA class I and II alleles and haploType wiTh auTism: a case conTrol sTury[J]. AuTism Res TreaT, 2014, 2014: 242048.
[47]
ATladóTTir HO, Thorsen P, ØsTergaard L, eT al. MaTernal infecTion requiring hospiTalizaTion during pregnancy and auTism specTrum disorders[J]. J AuTism Dev Disord, 2010, 40(12): 1423-1430.
