Autism spectrum disorders and natural killer cells: a review on pathogenesis and treatment

References

• Constantino JN, Marrus N. The early origins of autism. Child Adolesc Psychiatr Clin N Am. 2017 Jul;26(3):555–570.
   PubMed Web of Science ®Google Scholar
• Dawson G, Meltzoff AN, Osterling J, et al. Children with autism fail to orient to naturally occurring social stimuli. J Autism Dev Disord. 1998 Dec;28(6):479–485.
   PubMed Web of Science ®Google Scholar
• Kanner L. Autistic disturbances of affective contact. Acta Paedopsychiatr. 1968;35(4):100–136.
   PubMedGoogle Scholar
• Vahia VN. Diagnostic and statistical manual of mental disorders 5: A quick glance. Indian J Psychiatry. 2013 Jul;55(3):220–223.
   PubMed Web of Science ®Google Scholar
• Maenner M, Shaw K, Baio J, et al. Prevalence of autism spectrum disorder among children aged 8 years — autism and developmental disabilities monitoring network, 11 Sites, United States, 2016. MMWR Surveillance Summaries. 2020;03/27(69):1–12.
   Google Scholar
• Werling DM, Geschwind DH. Sex differences in autism spectrum disorders. Curr Opin Neurol. 2013;26(2):146–153.
   PubMed Web of Science ®Google Scholar
• Halladay AK, Bishop S, Constantino JN, et al. Sex and gender differences in autism spectrum disorder: summarizing evidence gaps and identifying emerging areas of priority. Mol Autism. 2015;6:36.
   PubMed Web of Science ®Google Scholar
• Baxter AJ, Brugha TS, Erskine HE, et al. The epidemiology and global burden of autism spectrum disorders. Psychol Med. 2015 Feb;45(3):601–613.
   PubMed Web of Science ®Google Scholar
• Ashwood P, Wills S, Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol. 2006 Jul;80(1):1–15.
   PubMed Web of Science ®Google Scholar
• Barakonyi A, Rabot M, Marie-Cardine A, et al. Cutting edge: engagement of CD160 by its HLA-C physiological ligand triggers a unique cytokine profile secretion in the cytotoxic peripheral blood NK cell subset. J Immunol. 2004 Nov 1;173(9):5349–5354.
   PubMed Web of Science ®Google Scholar
• Odell D, Maciulis A, Cutler A, et al. Confirmation of the association of the C4B null allele in autism. Hum Immunol. 2005 Feb;66(2):140–145.
   PubMed Web of Science ®Google Scholar
• Stubbs EG. Autistic children exhibit undetectable hemagglutination-inhibition antibody titers despite previous rubella vaccination. J Autism Child Schizophr. 1976 Sep; 6(3):269–274.
   PubMedGoogle Scholar
• Chess S. Follow-up report on autism in congenital rubella. J Autism Child Schizophr. 1977 Mar; 7(1):69–81.
   PubMedGoogle Scholar
• Goto M, Tanimoto K, Chihara T, et al. Natural cell-mediated cytotoxicity in Sjogren’s syndrome and rheumatoid arthritis. Arthritis Rheum. 1981 Nov;24(11):1377–1382.
   PubMedGoogle Scholar
• Herberman RB, Ortaldo JR. Natural killer cells: their roles in defenses against disease. Science. 1981 Oct 2;214(4516):24–30.
   PubMed Web of Science ®Google Scholar
• Jie HB, Sarvetnick N. The role of NK cells and NK cell receptors in autoimmune disease. Autoimmunity. 2004 Mar;37(2):147–153.
   PubMed Web of Science ®Google Scholar
• Lit L, Gilbert DL, Walker W, et al. A subgroup of Tourette’s patients overexpress specific natural killer cell genes in blood: a preliminary report. Am J Med Genet B Neuropsychiatr Genet. 2007 Oct 5;144b(7):958–963.
   PubMed Web of Science ®Google Scholar
• Yovel G, Sirota P, Mazeh D, et al. Higher natural killer cell activity in schizophrenic patients: the impact of serum factors, medication, and smoking. Brain Behav Immun. 2000 Sep;14(3):153–169.
   PubMed Web of Science ®Google Scholar
• Filosi M, Kam-Thong T, Essioux L, et al. Transcriptome signatures from discordant sibling pairs reveal changes in peripheral blood immune cell composition in autism spectrum disorder. Transl Psychiatry. 2020 April 14;10(1):106.
   PubMed Web of Science ®Google Scholar
• Maeyama K, Tomioka K, Nagase H, et al. Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder: systematic Review and Meta-Analysis. J Autism Dev Disord. 2018 May;48(5):1483–1491.
   PubMed Web of Science ®Google Scholar
• Gentile I, Zappulo E, Riccio MP, et al. Prevalence of congenital cytomegalovirus infection assessed through viral genome detection in dried blood spots in children with autism spectrum disorders. In vivo (Athens, Greece). 2017 May-Jun 31;3:467–473.
   PubMed Web of Science ®Google Scholar
• Goodier MR, Jonjić S, Riley EM, et al. CMV and natural killer cells: shaping the response to vaccination. Eur J Immunol. 2018 Jan;48(1):50–65.
   PubMed Web of Science ®Google Scholar
• Wang HZ, Qin HD, Guo W, et al. New insights into the genetic mechanism of IQ in autism spectrum disorders. Front Genet. 2013;4:195.
   PubMedGoogle Scholar
• Enstrom AM, Lit L, Onore CE, et al. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav Immun. 2009 Jan;23(1):124–133.
   PubMed Web of Science ®Google Scholar
• 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 Neuroimmunol. 2008 Dec 15;205(1–2):148–154.
   PubMed Web of Science ®Google Scholar
• Bennabi M, Tarantino N, Gaman A, et al. Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders: stigma/consequence of unresolved early infectious events? Mol Autism. 2019;10:22.
   PubMed Web of Science ®Google Scholar
• Warren RP, Foster A, Margaretten NC. Reduced natural killer cell activity in autism. J Am Acad Child Adolesc Psychiatry. 1987 May;26(3):333–335.
   PubMed Web of Science ®Google Scholar
• Pradeu T, Jaeger S, Vivier E. The speed of change: towards a discontinuity theory of immunity? Nat Rev Immunol. 2013 Oct;13(10):764–769.
   PubMed Web of Science ®Google Scholar
• Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol. 2015;7(1):a020412–a020412.
   PubMed Web of Science ®Google Scholar
• Fiorentino M, Sapone A, Senger S, et al. Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016 Nov 29;7(1):49.
   PubMedGoogle Scholar
• Cooper MA, Fehniger TA, Ponnappan A, et al. Interleukin-1beta costimulates interferon-gamma production by human natural killer cells. Eur J Immunol. 2001 Mar;31(3):792–801.
   PubMed Web of Science ®Google Scholar
• Goines PE, Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicol Teratol. 2013 Mar-Apr;36:67–81.
   PubMed Web of Science ®Google Scholar
• Masi A, Quintana DS, Glozier N, et al. Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry. 2015 April 01;20(4):440–446.
   PubMed Web of Science ®Google Scholar
• Emanuele E, Orsi P, Boso M, et al. Low-grade endotoxemia in patients with severe autism. Neurosci Lett. 2010 Mar 8;471(3):162–165.
   PubMed Web of Science ®Google Scholar
• Manzardo AM, Henkhaus R, Dhillon S, et al. Plasma cytokine levels in children with autistic disorder and unrelated siblings. Int J Dev Neurosci. 2012;30(2):121–127.
   PubMed Web of Science ®Google Scholar
• Wu H, Wang X, Gao J, et al. Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism. Life Sci. 2017 Mar 15;173:43–54.
   PubMed Web of Science ®Google Scholar
• Hegazy HG, Ali EHA, Elgoly AHM. Interplay between pro-inflammatory cytokines and brain oxidative stress biomarkers: evidence of parallels between butyl paraben intoxication and the valproic acid brain physiopathology in autism rat model. Cytokine. 2015 Feb 01;71(2):173–180.
   PubMed Web of Science ®Google Scholar
• Lucchina L, Depino AM. Altered peripheral and central inflammatory responses in a mouse model of autism. Autism Res. 2014 Apr;7(2):273–289.
   PubMed Web of Science ®Google Scholar
• Abdallah MW, Larsen N, Mortensen EL, et al. Neonatal levels of cytokines and risk of autism spectrum disorders: an exploratory register-based historic birth cohort study utilizing the Danish newborn screening biobank. J Neuroimmunol. 2012 Nov 15;252(1–2):75–82.
   PubMed Web of Science ®Google Scholar
• Presta I, Vismara M, Novellino F, et al. Innate immunity cells and the neurovascular unit. Int J Mol Sci. 2018;19(12):3856.
   Web of Science ®Google Scholar
• Ashwood P, Corbett BA, Kantor A, et al. In search of cellular immunophenotypes in the blood of children with autism. PloS One. 2011 May 4;6(5):e19299.
   PubMed Web of Science ®Google Scholar
• Saresella M, Marventano I, Guerini FR, et al. An autistic endophenotype results in complex immune dysfunction in healthy siblings of autistic children. Biol Psychiatry. 2009 Nov 15;66(10):978–984.
   PubMed Web of Science ®Google Scholar
• Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001 Nov;22(11):633–640.
   PubMed Web of Science ®Google Scholar
• Comans-Bitter WM, de Groot R, van den Beemd R, et al. Immunophenotyping of blood lymphocytes in childhood reference values for lymphocyte subpopulations. J Pediatr. 1997 May 01;130(3):388–393.
   PubMed Web of Science ®Google Scholar
• López-Cacho JM, Gallardo S, Posada M, et al. Characterization of immune cell phenotypes in adults with autism spectrum disorders. J Invest Med. 2016;64(7):1179.
   PubMed Web of Science ®Google Scholar
• Trowsdale J, Barten R, Haude A, et al. The genomic context of natural killer receptor extended gene families. Immunol Rev. 2001 Jun;181:20–38.
   PubMed Web of Science ®Google Scholar
• Torres AR, Westover JB, Gibbons C, et al. Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism. Brain Behav Immun. 2012 Oct;26(7):1122–1127.
   PubMed Web of Science ®Google Scholar
• Ansel A, Rosenzweig JP, Zisman PD, et al. Variation in gene expression in autism spectrum disorders: an extensive review of transcriptomic studies. Front Neurosci. 2016;10:601.
   PubMed Web of Science ®Google Scholar
• Geschwind DH, State MW. Gene hunting in autism spectrum disorder: on the path to precision medicine. Lancet Neurol. 2015 Nov;14(11):1109–1120.
   PubMed Web of Science ®Google Scholar
• Torres AR, Sweeten TL, Johnson RC, et al. Common genetic variants found in HLA and KIR immune genes in autism spectrum disorder. Front Neurosci. 2016;10:463.
   PubMed Web of Science ®Google Scholar
• Harville T, Rhodes-Clark B, Bennuri SC, et al. Inheritance of HLA-Cw7 associated with autism spectrum disorder (ASD) [Original Research]. Front Psychiatry. 2019 September 11;10(612). DOI:https://doi.org/10.3389/fpsyt.2019.00612
   Google Scholar
• Yelavarthi KK, Fishback JL, Hunt JS. Analysis of HLA-G mRNA in human placental and extraplacental membrane cells by in situ hybridization. J Immunol. 1991 Apr 15;146(8):2847–2854.
   PubMed Web of Science ®Google Scholar
• van Wijk IJ, Griffioen S, Tjoa ML, et al. HLA-G expression in trophoblast cells circulating in maternal peripheral blood during early pregnancy. Am J Obstet Gynecol. 2001 Apr;184(5):991–997.
   PubMed Web of Science ®Google Scholar
• Favier B, Lemaoult J, Lesport E, et al. ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the late but not the early events of the NK-cell activating synapse. Faseb J. 2010 Mar;24(3):689–699.
   PubMed Web of Science ®Google Scholar
• Akhter A, Faridi RM, Das V, et al. In vitro up-regulation of HLA-G using dexamethasone and hydrocortisone in first-trimester trophoblast cells of women experiencing recurrent miscarriage. Tissue Antigens. 2012 Aug;80(2):126–135.
   PubMedGoogle Scholar
• Hviid TV, Hylenius S, Hoegh AM, et al. HLA-G polymorphisms in couples with recurrent spontaneous abortions. Tissue Antigens. 2002 Aug;60(2):122–132.
   PubMedGoogle Scholar
• Nardi Fda S, Slowik R, Wowk PF, et al. Analysis of HLA-G polymorphisms in couples with implantation failure. Am J Reproduct Immunol. 2012 Dec;68(6):507–514.
   PubMed Web of Science ®Google Scholar
• Guerini FR, Bolognesi E, Sotgiu S, et al. HLA-G allelic distribution in Sardinian children with Autism spectrum disorders: A replication study. Brain Behav Immun. 2019 Jul;79:314–318.
   PubMed Web of Science ®Google Scholar
• Caocci G, Greco M, Arras M, et al. HLA-G molecules and clinical outcome in chronic myeloid leukemia. Leuk Res. 2017 Oct;61:1–5.
   PubMed Web of Science ®Google Scholar
• Patterson PH. Maternal infection and immune involvement in autism. Trends Mol Med. 2011 Jul;17(7):389–394.
   PubMed Web of Science ®Google Scholar
• Fu B, Zhou Y, Ni X, et al. Natural killer cells promote fetal development through the secretion of growth-promoting factors. Immunity. 2017 Dec 19;47(6):1100–1113.e6.
   PubMed Web of Science ®Google Scholar
• Guerini FR, Bolognesi E, Chiappedi M, et al. Activating KIR molecules and their cognate ligands prevail in children with a diagnosis of ASD and in their mothers. Brain Behav Immun. 2014 Feb;36:54–60.
   PubMed Web of Science ®Google Scholar
• Gamliel M, Anderson KL, Ebstein RP, et al. Paternal HLA-C and maternal killer-cell immunoglobulin-like receptor genotypes in the development of autism. Front Pediatr. 2016;4:76.
   PubMed Web of Science ®Google Scholar
• Reddy M, Eirikis E, Davis C, et al. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J Immunol Methods. 2004 Oct;293(1–2):127–142.
   PubMed Web of Science ®Google Scholar
• Lopez-Cacho JM, Gallardo S, Posada M, et al. Characterization of immune cell phenotypes in adults with autism spectrum disorders. J Invest Med. 2016 Oct;64(7):1179–1185.
   PubMed Web of Science ®Google Scholar
• Stricker RB, Winger EE. Decreased CD57 lymphocyte subset in patients with chronic Lyme disease. Immunol Lett. 2001 Feb 1;76(1):43–48.
   PubMed Web of Science ®Google Scholar
• Wang EC, Borysiewicz LK. The role of CD8+, CD57+ cells in human cytomegalovirus and other viral infections. Scandinavian J Infec Dis Supplementum. 1995;99:69–77.
   PubMedGoogle Scholar
• Yssel H, Shanafelt MC, Soderberg C, et al. Borrelia burgdorferi activates a T helper type 1-like T cell subset in Lyme arthritis. J Exp Med. 1991 Sep 1;174(3):593–601.
   PubMed Web of Science ®Google Scholar
• Siniscalco D, Mijatovic T, Bosmans E, et al. Decreased numbers of CD57+CD3- cells identify potential innate immune differences in patients with autism spectrum disorder. In Vivo. 2016 Mar-Apr;30(2):83–89.
   PubMed Web of Science ®Google Scholar
• Abo T, Balch CM. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029.
   PubMed Web of Science ®Google Scholar
• Gunturi A, Berg RE, Forman J. The role of CD94/NKG2 in innate and adaptive immunity. Immunol Res. 2004;30(1):29–34.
   PubMed Web of Science ®Google Scholar
• Malmberg KJ, Beziat V, Ljunggren HG. Spotlight on NKG2C and the human NK-cell response to CMV infection. Eur J Immunol. 2012 Dec;42(12):3141–3145.
   PubMed Web of Science ®Google Scholar
• Virgin HW, Wherry EJ, Ahmed R. Redefining chronic viral infection. Cell. 2009 Jul 10;138(1):30–50.
   PubMed Web of Science ®Google Scholar
• Popa N, Cedile O, Pollet-Villard X, et al. RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres. Glia. 2011 Jan;59(1):35–44.
   PubMed Web of Science ®Google Scholar
• Gregg JP, Lit L, Baron CA, et al. Gene expression changes in children with autism. Genomics. 2008 Jan;91(1):22–29.
   PubMed Web of Science ®Google Scholar
• Clark HF, Gurney AL, Abaya E, et al. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265–2270.
   PubMed Web of Science ®Google Scholar
• Jia W, Li H, He YW. The extracellular matrix protein mindin serves as an integrin ligand and is critical for inflammatory cell recruitment. Blood. 2005 Dec 1;106(12):3854–3859.
   PubMed Web of Science ®Google Scholar
• He YW, Li H, Zhang J, et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat Immunol. 2004 Jan;5(1):88–97.
   PubMed Web of Science ®Google Scholar
• Walzer T, Jaeger S, Chaix J, et al. Natural killer cells: from CD3(-)NKp46(+) to post-genomics meta-analyses. Curr Opin Immunol. 2007 06; 19(3): 365–372.
   PubMed Web of Science ®Google Scholar
• Jounaidi Y, Cotten JF, Miller KW, et al. Tethering IL2 to Its Receptor IL2Rβ Enhances Antitumor Activity and Expansion of Natural Killer NK92 Cells. Cancer Res. 2017 Nov 1;77(21):5938–5951.
   PubMed Web of Science ®Google Scholar
• Zhang Z, Gothe F, Pennamen P, et al. Human interleukin-2 receptor β mutations associated with defects in immunity and peripheral tolerance. J Exp Med. 2019 Jun 3;216(6):1311–1327.
   PubMed Web of Science ®Google Scholar
• Tschopp J, Nabholz M. Perforin-mediated target cell lysis by cytolytic T lymphocytes. Annu Rev Immunol. 1990;8:279–302.
   PubMed Web of Science ®Google Scholar
• Willenbring RC, Johnson AJ. Finding a balance between protection and pathology: the dual role of perforin in human disease. Int J Mol Sci. 2017;18(8):1608.
   Web of Science ®Google Scholar
• Dichmann S, Herouy Y, Purlis D, et al. Fractalkine induces chemotaxis and actin polymerization in human dendritic cells. Inflamm Res. 2001 Nov;50(11):529–533.
   PubMed Web of Science ®Google Scholar
• Liu C, Hong K, Chen H, et al. Evidence for a protective role of the CX3CL1/CX3CR1 axis in a model of amyotrophic lateral sclerosis. Biol Chem. 2019;400:651.
   PubMed Web of Science ®Google Scholar
• Sunnemark D, Eltayeb S, Nilsson M, et al. CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin. J Neuroinflammation. 2005 Jul 29;2:17.
   PubMed Web of Science ®Google Scholar
• Soriano SG, Amaravadi LS, Wang YF, et al. Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury. J Neuroimmunol. 2002 Apr;125(1–2):59–65.
   PubMed Web of Science ®Google Scholar
• Infante-Duarte C, Weber A, Krätzschmar J, et al. Frequency of blood CX3CR1-positive natural killer cells correlates with disease activity in multiple sclerosis patients. Faseb J. 2005 Nov;19(13):1902–1904.
   PubMedGoogle Scholar
• Brumbaugh KM, Binstadt BA, Billadeau DD, et al. Functional role for Syk tyrosine kinase in natural killer cell-mediated natural cytotoxicity. J Exp Med. 1997 Dec 15;186(12):1965–1974.
   PubMed Web of Science ®Google Scholar
• Warren RP, Odell JD, Warren WL, et al. Brief report: immunoglobulin A deficiency in a subset of autistic subjects. J Autism Dev Disord. 1997 Apr;27(2):187–192.
   PubMed Web of Science ®Google Scholar
• Garcia-Laorden MI, Stroo I, Terpstra S, et al. Expression and function of granzymes A and B in escherichia coli peritonitis and sepsis. Mediators Inflamm. 2017;2017:4137563.
   PubMed Web of Science ®Google Scholar
• Nemeth MJ, Kirby MR, Bodine DM. Hmgb3 regulates the balance between hematopoietic stem cell self-renewal and differentiation. Proc Nat Acad Sci. 2006;103(37):13783.
   PubMed Web of Science ®Google Scholar
• Yanai H, Ban T, Wang Z, et al. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature. 2009 November 01;462(7269):99–103.
   PubMed Web of Science ®Google Scholar
• Dipasquale V, Cutrupi MC, Colavita L, et al. Neuroinflammation in Autism Spectrum Disorders: Role Of High Mobility Group Box 1 protein. Int J Mol Cell Med. 2017 Summer;6(3):148–155.
   PubMed Web of Science ®Google Scholar
• Sabry M, Zubiak A, Hood SP, et al. Tumor- and cytokine-primed human natural killer cells exhibit distinct phenotypic and transcriptional signatures. PloS One. 2019;14(6):e0218674–e0218674.
   PubMed Web of Science ®Google Scholar
• Ren X, Dong F, Zhuang Y, et al. Effect of neuromedin U on allergic airway inflammation in an asthma model (Review). Exp Ther Med. 2020 Feb 01;19(2):809–816.
   PubMed Web of Science ®Google Scholar
• Martinez VG, Neuromedin OL. U: a multifunctional neuropeptide with pleiotropic roles. Clin Chem. 2015 Mar;61(3):471–482.
   PubMed Web of Science ®Google Scholar
• Stamova BS, Tian Y, Nordahl CW, et al. Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders. Mol Autism. 2013 Sep 4;4(1):30.
   PubMedGoogle Scholar
• Jacobi C, Claus M, Wildemann B, et al. Exposure of NK cells to intravenous immunoglobulin induces IFN gamma release and degranulation but inhibits their cytotoxic activity. Clin Immunol. 2009 Dec;133(3):393–401.
   PubMed Web of Science ®Google Scholar
• Bunk S, Ponnuswamy P, Trbic A, et al. IVIG induces apoptotic cell death in CD56dim NK cells resulting in inhibition of ADCC effector activity of human PBMC. Clin Immunol. 2019 Jan 01;198:62–70.
   PubMed Web of Science ®Google Scholar
• Gupta S, Samra D, Adaptive AS. Innate immune responses in autism: rationale for therapeutic use of intravenous immunoglobulin. J Clin Immunol. 2010 May;30(Suppl 1):S90–6.
   PubMedGoogle Scholar
• Wong PH, White KM. Impact of immunoglobulin therapy in pediatric disease: a review of immune mechanisms. Clin Rev Allergy Immunol. 2016 Dec;51(3):303–314.
   PubMed Web of Science ®Google Scholar
• Gupta S, Aggarwal S, Heads C. Dysregulated immune system in children with autism: beneficial effects of intravenous immune globulin on autistic characteristics. J Autism Dev Disord. 1996 Aug;26(4):439–452.
   PubMed Web of Science ®Google Scholar
• Melamed IR, Heffron M, Testori A, et al. A pilot study of high-dose intravenous immunoglobulin 5% for autism: impact on autism spectrum and markers of neuroinflammation. Autism Res. 2018 Mar;11(3):421–433.
   PubMed Web of Science ®Google Scholar
• Plioplys AV. Intravenous immunoglobulin treatment of children with autism. J Child Neurol. 1998 Feb;13(2):79–82.
   PubMed Web of Science ®Google Scholar
• Vitale C, Chiossone L, Cantoni C, et al. The corticosteroid-induced inhibitory effect on NK cell function reflects down-regulation and/or dysfunction of triggering receptors involved in natural cytotoxicity. Eur J Immunol. 2004 Nov;34(11):3028–3038.
   PubMed Web of Science ®Google Scholar
• Duffy FH, Shankardass A, McAnulty GB, et al. Corticosteroid therapy in regressive autism: a retrospective study of effects on the frequency modulated auditory evoked response (FMAER), language, and behavior. BMC Neurol. 2014 May;15(14):70.
   Google Scholar
• Mg Lm C, Buchanan CP, Field-Chez M. Pulse high-dose steroids as combination therapy with valproic acid in epileptic aphasia patients with pervasive developmental delay or autism. InAnnals Neurol. 1998 Sep 1;44(3): 539. 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA: LIPPINCOTT WILLIAMS & WILKINS.
   Web of Science ®Google Scholar
• Chez MG, Guido-Estrada N. Immune therapy in autism: historical experience and future directions with immunomodulatory therapy. Neurotherapeutics. 2010;7(3):293–301.
   PubMed Web of Science ®Google Scholar
• Lewine J, Chez M, editors. Patterns of epileptiform activity and clinical response to steroid therapy in autism. International Meeting for Autism Research (IMFAR). Chicago Hilton and Towers. Chicago, IL. USA; 2009.
   Google Scholar
• Shenoy S, Arnold S, Chatila T. Response to steroid therapy in autism secondary to autoimmune lymphoproliferative syndrome. J Pediatr. 2000 May;136(5):682–687.
   PubMed Web of Science ®Google Scholar
• Sandler RH, Bolte ER, Chez MG, et al. Relief of psychiatric symptoms in a patient with Crohn’s disease after metronidazole therapy. Clin Infect Dis. 2000 Jan;30(1):213–214.
   PubMed Web of Science ®Google Scholar