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The role of maternal autoantibodies in the pathogenesis of autism spectrum disorders


Authors: I. Dudová 1;  K. Horáčková 2;  M. Hrdlička 1;  M. Balaštík 3
Authors‘ workplace: Dětská psychiatrická klinika 2. LF UK a FN Motol, Praha 1;  Psychiatrická klinika 1. LF UK a VFN, Praha 2;  Oddělení molekulární neurobiologie, Fyziologický ústav AV ČR, Praha 3
Published in: Čes-slov Pediat 2019; 74 (4): 205-210.
Category:

Overview

Autism spectrum disorders (ASD) are heterogeneous group of neurodevelopmental disorders characterized by impairments in social interaction, communication and stereotyped, repetitive patterns of behavior, interests and activities. The causes and risk factors of ASD are largely unknown with a complex etiology combining genetic as well as environmental factors. In the last two decades it has been well established that an important role in the prenatal brain development is played by the immune system. Deregulation of the immune system during embryonic development may lead to neurodevelopmental changes resulting in ASD and one of the potential etiologic factors in the development of ASD has been identified as presence of maternal autoantibodies targeting the fetal brain proteins. The type of ASD associated with the presence of maternal autoantibodies has been referred to as MAR autism (maternal antibodies related autism). The link between the maternal autoantibodies and ASD has been demonstrated in both clinical studies and animal models. Several protein targets of ASD-related maternal autoantibodies have been identified. In this article we focus on Collapsin response mediator protein 2 (CRMP2), which has been previously shown to play an important role in regulation of axon growth and guidance during brain development.

In addition, we discuss the potential effect of CRMP2 targeting by maternal antibodies in ASD pathogenesis and future possibilities of MAR ASD treatment.

Keywords:

therapy – Animal models – maternal autoantibodies – Autism spectrum disorder – CRMP2


Sources

1. Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res 2009; 65: 591–598.

2. DSM-5 – Diagnostický a statistický manuál duševních poruch. 1. české vydání. Praha: Hogrefe - Testcentrum, 2015.

3. Gaugler T, Klei L, Sanders SJ, et al. Most genetic risk for autism resides with common variation. Nat Genet 2014; 46 (8): 881–885.

4. Hrdlička M, Komárek V (eds). Dětský autismus: přehled současných poznatků. Vyd. 2., dopl. Praha: Portál, 2014.

5. Keil A, Daniels JL, Forssen U, et al. Parental autoimmune diseases associated with autism spectrum disorders in offspring. Epidemiology 2010; 21: 805–808.

6. Wu S, Ding Y, Wu F, et al. Family history of autoimmune diseases is associated with an increased risk of autism in children: A systematic review and meta-analysis. Neurosci Biobehav Rev 2015; 55: 322–332.

7. Atlandottir HO, Thorsen P, Ostergaard I, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord 2010; 40: 1423–1430.

8. Matelski L, Van de Water J. Risk factors in autism: Thinking outside the brain. J Autoimmun 2016; 67: 1–7.

9. Jones KL, Pride MC, Edmiston E, et al. Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism. Mol Psychiatry 2018 Jun 28. dog:10.1038/s41380-018-0126.1. [Epub ahead of print].

10. Braunschweig D, Krakowiak P, Duncanson P, et al. Autism-specific maternal autoantibodies recognize critical proteins in developing brain. Transl Psychiatry 2013; 3: e277.

11. Fox-Edmiston E, Van de Water J. Maternal anti-fetal brain IgG autoantibodies and autism spectrum disorder: current knowledge and its implications for potential therapeutics. CNS Drugs 2015; 29: 715–724.

12. Jones KL, Van de Water J. Maternal autoantibody related autism: mechanisms and pathways. Mol Psychiatry 2019; 24: 252–265.

13. Edmiston E, Ashwood P, Van de Water J. Autoimmunity, autoantibodies, and autism spectrum disorders (ASD). Biol Psychiatry 2017; 81 (5): 383–390.

14. Bagasra O, Heggen C. Autism and Environmental Factors. NJ: Wiley, 2018.

15. Karpiak SE Jr, Rapport MM. Behavioral changes 2-month-old rats following prenatal exposure to antibodies against synaptic membranes. Brain Res 1975; 92: 405–413.

16. Rick JT, Gregson AN, Leibowitz S, Adinolfi M. Behavioural changes in adult rats following administration of antibodies again brain gangliosides. Dev Med Child Neurol 1980; 22: 719–724.

17. Martin LA, Ashwood P, Braunschweig D, et al. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immune 2008; 22 (6): 806–816.

18. Bauman MD, Josif AM, Ashwood P, et al. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Transl Psychiatry 2013; 3: e278.

19. Singer HS, Morris C, Gause C, et al. Prenatal exposure to antibodies from mothers of children with autism produces neurobehavioral alterations: A pregnant dam mouse model. J Neuroimmunol 2009; 211 (1–2): 39–48.

20. Braunschweig D, Ashwood P, Krakowiak P, et al. Autism: Maternally derived antibodies specific for fetal brain proteins. Neurotoxicology 2008; 29: 226–231.

21. Croen LA, Braunschweig D. Maternal mid-pregnancy autoantibodies to fetal brain protein: the early markers for autism study. Biol Psychiatry 2008; 64: 583–588.

22. Braunschweig D, Duncaston P, Boyce R, et al. Behavioral correlates of maternal antibody status mong chidren with autism. J Autism Dev Disord 2011; 42: 1435–1445.

23. Courchesne E, Karns CM, Davis HR, et al. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 2001; 57: 245–254.

24. Nordahl CW, Lange N, Li DD, et al. Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders. Proc Natl Acad Sci U S A 2011; 108: 20195–20200.

25. Nordahl CW, Braunschweig D, Iosif AM, et al. Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder. Brain Behav Immun 2013; 30: 61–65.

26. Lin PC, Chan PM, Hall, C, Manser E. Collapsin response mediator proteins (CRMPs) are a new class of microtubule-associated protein (MAP) that selectively interacts with assembled microtubules via a taxol-sensitive binding interaction. J Biol Chem 2011; 286: 41466–41478.

27. Wang LH, Strittmatter SM. A family of rat CRMP genes is differentially expressed in the nervous system. J Neurosci 1996; 16: 6197–6207.

28. Škrlantová A. Změny fosforylace proteinu CRMP2 spjaté s patogenezí Alzheimerovy choroby a jejich vliv na funkci neuronů. Bakalářská práce. Praha: Univerzita Karlova v Praze. Přírodovědecká fakulta, 2015.

29. Nakamura H, Yamashita N, Kimura A, et al. Comprehensive behavioral study and proteomic analyses of CRMP2-deficient mice. Genes Cells 2016; 21: 1059–1079.

30. Gu Y, Hamajima N, Ihara Y. Neurofibrillary tangle-associated collapsing response mediator protein-2 (CRMP-2) is highly phosphorylated on The-509, Ser-518, and Ser-522. Biochemistry 2000; 39: 4267–4275.

31. Cole AR, Soutar MPM, Rembutsu M, et al. Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer`s disease progression. J Neurochem 2007; 103: 1132–1144.

32. Yuasa-Kawada J, Suzuko R, Kano F, et al. Axonal morphogenesis controlled by antagonistic roles of two CRMP subtypes in microtubule organization. Eur J Neurosci 2003; 17: 2329–2343.

33. Bretin S, Reibel S, Charrier E, et al. Differential expression of CRMP1, CRMP2A, CRMP2B, and CRMP5 in axons or dendrites of distinct neurons in the mouse brain. J Comp Neurol 2005; 486: 1–17.

34. Balastik M, Zhou XZ, Alberich-Jorda M, et al. Prolyl isomerase Pin1 regulates axon guidance by stabilizing CRMP2A selectively in distal axons. Cell Rep 2015; 13 (4): 812–828.

35. Bednařík J. Léčebná výměnná plazmaferéza v léčbě autoimunitních nervosvalových onemocnění. Neurol praxi 2011; 12 (6): 394–397.

36. 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): 1283–1288.

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Neonatology Paediatrics General practitioner for children and adolescents
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