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Published in: CNS Drugs 9/2015

01-09-2015 | Leading Article

Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum Disorder: Current Knowledge and its Implications for Potential Therapeutics

Authors: Elizabeth Fox-Edmiston, Judy Van de Water

Published in: CNS Drugs | Issue 9/2015

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Abstract

Several studies have found a correlation between the presence of circulating maternal autoantibodies and neuronal dysfunction in the neonate. Specifically, maternal anti-brain autoantibodies, which may access the fetal compartment during gestation, have been identified as one risk factor for developing autism spectrum disorder (ASD). Studies by our laboratory elucidated seven neurodevelopmental proteins recognized by maternal autoantibodies whose presence is associated with a diagnosis of maternal autoantibody-related (MAR) autism in the child. While the specific process of anti-brain autoantibody generation is unclear and the detailed pathogenic mechanisms are currently unknown, identification of the maternal autoantibody targets increases the therapeutic possibilities. The potential therapies discussed in this review provide a framework for possible future medical interventions.
Literature
2.
go back to reference Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect. 2006;114(7):1119–25. Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect. 2006;114(7):1119–25.
7.
9.
go back to reference Garty BZ, Ludomirsky A, Danon YL, Peter JB, Douglas SD. Placental transfer of immunoglobulin G subclasses. Clin Diagn Lab Immunol. 1994;1(6):667–9.PubMedCentralPubMed Garty BZ, Ludomirsky A, Danon YL, Peter JB, Douglas SD. Placental transfer of immunoglobulin G subclasses. Clin Diagn Lab Immunol. 1994;1(6):667–9.PubMedCentralPubMed
12.
18.
go back to reference Brimberg L, Sadiq A, Gregersen PK, Diamond B. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder. Mol Psychiatry. 2013;18(11):1171–7.CrossRefPubMed Brimberg L, Sadiq A, Gregersen PK, Diamond B. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder. Mol Psychiatry. 2013;18(11):1171–7.CrossRefPubMed
21.
go back to reference Atladóttir HÓ, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, et al. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics. 2009;124(2):687–94. doi:10.1542/peds.2008-2445.CrossRefPubMed Atladóttir HÓ, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, et al. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics. 2009;124(2):687–94. doi:10.​1542/​peds.​2008-2445.CrossRefPubMed
25.
go back to reference Mylona E, Melissaris S, Giannopoulou I, Theohari I, Papadimitriou C, Keramopoulos A, et al. Y-box-binding protein 1 (YB1) in breast carcinomas: relation to aggressive tumor phenotype and identification of patients at high risk for relapse. Eur J Surg Oncol. 2014;40(3):289–96. doi:10.1016/j.ejso.2013.09.008.CrossRefPubMed Mylona E, Melissaris S, Giannopoulou I, Theohari I, Papadimitriou C, Keramopoulos A, et al. Y-box-binding protein 1 (YB1) in breast carcinomas: relation to aggressive tumor phenotype and identification of patients at high risk for relapse. Eur J Surg Oncol. 2014;40(3):289–96. doi:10.​1016/​j.​ejso.​2013.​09.​008.CrossRefPubMed
28.
go back to reference Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immun. 2008;22(6):806–16. doi:10.1016/j.bbi.2007.12.007. Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immun. 2008;22(6):806–16. doi:10.​1016/​j.​bbi.​2007.​12.​007.
29.
30.
go back to reference Braunschweig D, Golub MS, Koenig CM, Qi L, Pessah IN, Van de Water J, et al. Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model. J Neuroimmunol. 2012;252(1):56–65. Braunschweig D, Golub MS, Koenig CM, Qi L, Pessah IN, Van de Water J, et al. Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model. J Neuroimmunol. 2012;252(1):56–65.
31.
32.
go back to reference Martínez-Cerdeño V, Camacho J, Fox E, Miller E, Ariza J, Kienzle D, et al. Prenatal exposure to autism-specific maternal autoantibodies alters proliferation of cortical neural precursor cells, enlarges brain, and increases neuronal size in adult animals. Cerebral Cortex. 2014. doi:10.1093/cercor/bhu291 (Epub 2014 Dec 22).PubMed Martínez-Cerdeño V, Camacho J, Fox E, Miller E, Ariza J, Kienzle D, et al. Prenatal exposure to autism-specific maternal autoantibodies alters proliferation of cortical neural precursor cells, enlarges brain, and increases neuronal size in adult animals. Cerebral Cortex. 2014. doi:10.​1093/​cercor/​bhu291 (Epub 2014 Dec 22).PubMed
41.
go back to reference Vaccaro C, Zhou J, Ober RJ, Ward ES. Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Nat Biotechnol. 2005;23(10):1283–8.CrossRefPubMed Vaccaro C, Zhou J, Ober RJ, Ward ES. Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Nat Biotechnol. 2005;23(10):1283–8.CrossRefPubMed
42.
go back to reference Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat Rev Immunol. 2013;13(3):176–89.CrossRefPubMed Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat Rev Immunol. 2013;13(3):176–89.CrossRefPubMed
45.
go back to reference Murphy K. Janeway’s immunobiology. 8th ed. New York: Garland Science; 2011. Murphy K. Janeway’s immunobiology. 8th ed. New York: Garland Science; 2011.
47.
go back to reference Smith SEP, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007;27(40):10695–702.PubMedCentralCrossRefPubMed Smith SEP, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007;27(40):10695–702.PubMedCentralCrossRefPubMed
48.
go back to reference Neubert K, Meister S, Moser K, Weisel F, Maseda D, Amann K, et al. The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat Med. 2008;14(7):748–55.CrossRefPubMed Neubert K, Meister S, Moser K, Weisel F, Maseda D, Amann K, et al. The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat Med. 2008;14(7):748–55.CrossRefPubMed
49.
go back to reference Ichikawa HT, Conley T, Muchamuel T, Jiang J, Lee S, Owen T, et al. Beneficial effect of novel proteasome inhibitors in murine lupus via dual inhibition of type I interferon and autoantibody-secreting cells. Arthritis Rheum. 2012;64(2):493–503. doi:10.1002/art.33333.PubMedCentralCrossRefPubMed Ichikawa HT, Conley T, Muchamuel T, Jiang J, Lee S, Owen T, et al. Beneficial effect of novel proteasome inhibitors in murine lupus via dual inhibition of type I interferon and autoantibody-secreting cells. Arthritis Rheum. 2012;64(2):493–503. doi:10.​1002/​art.​33333.PubMedCentralCrossRefPubMed
Metadata
Title
Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum Disorder: Current Knowledge and its Implications for Potential Therapeutics
Authors
Elizabeth Fox-Edmiston
Judy Van de Water
Publication date
01-09-2015
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 9/2015
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-015-0279-2

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