Skip to main content

Advertisement

SpringerLink
Log in

How Relevant are GFAP Autoantibodies in Autism and Tourette Syndrome?

  • Original Paper
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

Controversy exists over the role of autoantibodies to central nervous system antigens in autism and Tourette Syndrome. We investigated plasma autoantibody titers to glial fibrillary acidic protein (GFAP) in children with classic onset (33) and regressive onset (26) autism, controls (25, healthy age- and gender-matched) and individuals with Tourette Syndrome (24) by enzyme-linked immunosorbent assays. We found a significant difference in autoantibody titers to GFAP, not accounted for by age, between the Tourette (significantly lower) and regressive autism groups. However, no differences were found between: classic/regressive; classic/controls; classic/Tourette; regressive/controls; or controls/Tourette. Autoantibody responses against GFAP are unlikely to play a pathogenic role in autism or Tourette Syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (4th ed.). Text Revision. Washington, DC.

  • Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995). Autism as a strongly genetic disorder: Evidence from a British twin study. Psychology of Medicine, 25, 63–77.

    Article  CAS  Google Scholar 

  • Borenstein, M., Rothstein, H., & Cohen, J. (2000). Power and Precision, version 2.0. www.PowerAndPrecision.com.

  • Chakrabarti, S., & Fombonne, E. (2001). Pervasive developmental disorders in preschool children. Journal of the American Medical Association, 285, 3093–3099.

    Article  PubMed  CAS  Google Scholar 

  • Coleman, M., & Gillberg, C. (1985). The biology of the autistic syndromes. New York: Praeger Publishers.

    Google Scholar 

  • Comi, A. M., Zimmerman, A. W., Frye, V. H., Law, P. A., & Peeden, J. N. (1999). Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. Journal of Child Neurology, 14, 388–394.

    PubMed  CAS  Google Scholar 

  • Connolly, A. M., Chez, M. G., Pestronk, A., Arnold, S. T., Mehta, S., & Deuel, R. K. (1999). Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders. Journal of Pediatrics, 134, 607–613.

    Article  PubMed  CAS  Google Scholar 

  • Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Van de Water, J. (2005). Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: A case-control study. Archives of Pediatrics, & Adolescent Medicine, 159, 151–157.

    Article  Google Scholar 

  • Dahl, D., Crosby, C. J., Gardner, E. E., & Bignami, A. (1982). Purification of the glial fibrillary acidic protein by anion-exchange chromatography. Analytical Biochemistry, 126, 165–169.

    Article  PubMed  CAS  Google Scholar 

  • Eng, L. F., Ghirnikar, R. S., & Lee, Y. L. (2000). Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochemical Research, 25, 1439–1451.

    Article  PubMed  CAS  Google Scholar 

  • Fombonne, E. (2003). The prevalence of autism. Journal of the American Medical Association, 289, 87–89.

    Article  PubMed  Google Scholar 

  • Fujinami, R. S., Zurbriggen, A., & Powell, H. C. (1988). Monoclonal antibody defines determinant between Theiler’s virus and lipid-like structures. Journal of Neuroimmunology, 20, 25–32.

    Article  PubMed  CAS  Google Scholar 

  • Gillberg, C., & Wing, L. (1999). Autism: Not an extremely rare disorder. Acta Psychiatra Scandinavica, 99, 399–406.

    Article  CAS  Google Scholar 

  • Goldberg, W. A., Osann, K., Filipek, P. A., Laulhere, T., Jarvis, K., Modahl, C., Flodman, P., & Spence, M. A. (2003). Language and other regression: assessment and timing. Journal of Autism and Developmental Disorders, 33, 607–616.

    Article  PubMed  Google Scholar 

  • Hallett, J. J., Harling-Berg, C. J., Knopf, P. M., Stopa, E. G., & Kiessling, L. S. (2000). Anti-striatal antibodies in Tourette syndrome cause neuronal dysfunction. Journal of Neuroimmunology, 111, 195–202.

    Article  PubMed  CAS  Google Scholar 

  • Hickey, W. F. (2001). Basic principles of immunological surveillance of the normal central nervous system. Glia, 36, 118–124.

    Article  PubMed  CAS  Google Scholar 

  • Jankovic, J. (2001). Tourette’s syndrome. New England Journal of Medicine, 345, 1184–1192.

    Article  PubMed  CAS  Google Scholar 

  • Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., Williamson, D., & Ryan, N. (1997). Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 980–988.

    Article  CAS  Google Scholar 

  • Kiessling, L. S., Marcotte, A. C., & Culpepper, L. (1993). Antineuronal antibodies in movement disorders. Pediatrics, 92, 39–43.

    PubMed  CAS  Google Scholar 

  • Lee, L. C., Zachary, A. A., Leffell, M. S., Newschaffer, C. J., Matteson, K. J., Tyler, J. D., & Zimmerman, A. W. (2006). HLA-DR4 in families with autism. Pediatric Neurology, 35, 303–307.

    Article  PubMed  Google Scholar 

  • Loiselle, C. R., Lee, O., Moran, T. H., & Singer, H. S. (2004). Striatal microinfusion of Tourette syndrome and PANDAS sera: failure to induce behavioral changes. Movement Disorders, 19, 390–396.

    Article  PubMed  Google Scholar 

  • Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Jr., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000). The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30, 205–223.

    Article  PubMed  CAS  Google Scholar 

  • Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview-revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685.

    Article  PubMed  CAS  Google Scholar 

  • Luyster, R., Richler, J., Risi, S., Hsu, W.-L., Dawson, G., Bernier, R., Dunn, M., Hepburn, S., Hyman, S. L., McMahon, W. M., Goudie-Nice, J., Minshew, N., Rogers, S., Sigman, M., Spence, M. A., Goldberg, W. A., Tager-Flusberg, H., Volkmar, F. R., & Lord, C. (2005). Early regression in social communication in autism spectrum disorders: A CPEA Study. Developmental Neuropsychology, 27, 311–336.

    Article  PubMed  Google Scholar 

  • Meinl, E., Krumbholz, M., & Hohlfeld, R. (2006). B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Annals of Neurology, 59, 880–892.

    Article  PubMed  CAS  Google Scholar 

  • Nelson, K. B. (1991). Prenatal and perinatal factors in the etiology of autism. Pediatrics, 87, 761–766.

    PubMed  CAS  Google Scholar 

  • Plioplys, A. V., Greaves, A., Kazemi, K., & Silverman, E. (1994). Immunoglobin reactivity in autism and Rett’s syndrome. Developmental Brain Dysfunction, 7, 12–16.

    Google Scholar 

  • Sambrook, J., Fritsch, E. F., & Maniatis, T. (1989). Molecular cloning: A laboratory manual. New York: Cold Spring Harbor Laboratory.

    Google Scholar 

  • Schotte, A., Janssen, P. F., Megens, A. A., & Leysen, J. E. (1993). Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography. Brain Research, 631, 191–202.

    Article  PubMed  CAS  Google Scholar 

  • Silva, S. C., Correia, C., Fesel, C., Barreto, M., Coutinho, A. M., Marques, C., Miguel, T. S., Ataide, A., Bento, C., Borges, L., Oliveira, G., & Vicente, A. M. (2004). Autoantibody repertoires to brain tissue in autism nuclear families. Journal of Neuroimmunology, 152, 176–182.

    Article  PubMed  CAS  Google Scholar 

  • Singer, H. S., Giuliano, J. D., Hansen, B. H., Hallett, J. J., Laurino, J. P., Benson, M., & Kiessling, L. S. (1998). Antibodies against human putamen in children with Tourette syndrome. Neurology, 50, 1618–1624.

    PubMed  CAS  Google Scholar 

  • Singer, H. S., Mink, J. W., Loiselle, C. R., Burke, K. A., Ruchkina, I., Morshed, S., Parveen, S., Leckman, J. F., Hallett, J. J., & Lombroso, P. J. (2005). Microinfusion of antineuronal antibodies into rodent striatum: failure to differentiate between elevated and low titers. Journal of Neuroimmunology, 163, 8–14.

    Article  PubMed  CAS  Google Scholar 

  • Singer, H. S., Morris, C. M., Williams, P. N., Yoon, D. Y., Hong, J. J., & Zimmerman, A. W. (2006). Antibrain antibodies in children with autism and their unaffected siblings. Journal of Neuroimmunology, 178, 149–155.

    Article  PubMed  CAS  Google Scholar 

  • Singh, V. K., & Rivas, W. H. (2004). Prevalence of serum antibodies to caudate nucleus in autistic children. Neuroscience Letters, 355, 53–56.

    Article  PubMed  CAS  Google Scholar 

  • Singh, V. K., Warren, R., Averett, R., & Ghaziuddin, M. (1997). Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatric Neurology, 17, 88–90.

    Article  PubMed  CAS  Google Scholar 

  • Singh, V. K., Warren, R. P., Odell, J. D., Warren, W. L., & Cole, P. (1993). Antibodies to myelin basic protein in children with autistic behavior. Brain Behavior and Immunity, 7, 97–103.

    Article  CAS  Google Scholar 

  • Swedo, S. E., Leonard, H. L., Garvey, M., Mittleman, B., Allen, A. J., Perlmutter, S., Lougee, L., Dow, S., Zamkoff, J., & Dubbert, B. K. (1998). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases. American Journal of Psychiatry, 155, 264–271.

    PubMed  CAS  Google Scholar 

  • Sweeten, T. L., Bowyer, S. L., Posey, D. J., Halberstadt, G. M., & McDougle, C. J. (2003). Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics, 112, e420.

    Article  PubMed  Google Scholar 

  • Taylor, J. R., Morshed, S. A., Parveen, S., Mercadante, M. T., Scahill, L., Peterson, B. S., King, R. A., Leckman, J. F., & Lombroso, P. J. (2002). An animal model of Tourette’s syndrome. American Journal of Psychiatry, 159, 657–660.

    Article  PubMed  Google Scholar 

  • Todd, R. D., Hickok, J. M., Anderson, G. M., & Cohen, D. J. (1988). Antibrain antibodies in infantile autism. Biological Psychiatry, 23, 644–647.

    Article  PubMed  CAS  Google Scholar 

  • Tolley, N. D., Tsunoda, I., & Fujinami, R. S. (1999). DNA vaccination against Theiler’s murine encephalomyelitis virus leads to alterations in demyelinating disease. Journal of Virology, 73, 993–1000.

    PubMed  CAS  Google Scholar 

  • Torres, A. R., Maciulis, A., Stubbs, E. G., Cutler, A., & Odell, D. (2002). The transmission disequilibrium test suggests that HLA-DR4 and DR13 are linked to autism spectrum disorder. Human Immunology, 63, 311–316.

    Article  PubMed  CAS  Google Scholar 

  • Torres, A. R., Sweeten, T. L., Cutler, A., Bedke, B. J., Fillmore, M., Stubbs, E. G., & Odell, D. (2006). The association and linkage of the HLA-A2 class I allele with autism. Human Immunology, 67, 346–351.

    Article  PubMed  CAS  Google Scholar 

  • Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57, 67–81.

    Article  PubMed  CAS  Google Scholar 

  • Vojdani, A., Campbell, A. W., 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. Journal of Neuroimmunology, 129, 168–177.

    Article  PubMed  CAS  Google Scholar 

  • Warren, R. P., Odell, J. D., Warren, W. L., Burger, R. A., Maciulis, A., Daniels, W. W., & Torres, A. R. (1996). Strong association of the third hypervariable region of HLA-DR β1 with autism. Journal of Neuroimmunology, 67, 97–102.

    Article  PubMed  CAS  Google Scholar 

  • Yamada, M., Zurbriggen, A., Oldstone, M. B. A., & Fujinami, R. S. (1991). Common immunologic determinant between human immunodeficiency virus type 1 gp41 and astrocytes. Journal of Virology, 65, 1370–1376.

    PubMed  CAS  Google Scholar 

  • Yeargin-Allsopp, M., Rice, C., Karapurkar, T., Doernberg, N., Boyle, C., & Murphy, C. (2003). Prevalence of autism in a US metropolitan area. Journal of the American Medical Association, 289, 49–55.

    Article  PubMed  Google Scholar 

  • Yeh, C. -B., Wu, C. -H., Tsung, H. -C., Chen, C. -W., Shyu, J. -F., & Leckman, J. F. (2006). Antineural antibody in patients with Tourette’s syndrome and their family members. Journal of Biomedical Science, 13, 101–112.

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman, A. W., Connors, S. L., Matteson, K. J., Lee, L. C., Singer, H. S., Castaneda, J. A., & Pearce, D. A. (2007). Maternal antibrain antibodies in autism. Brain Behavior and Immunity, 21, 351–357.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We wish to acknowledge Sarah E. Doyle, BS, M. Michal Peterson, BS and Nancy K. Burgess, BS, for excellent technical assistance, Ikuo Tsunoda, MD, PhD, for many helpful discussions and Kathleen Borick for the outstanding preparation of the manuscript. This work was supported by NIH U19 D/DC35476, which is part of the NICHD/NIDCD Collaborative Programs for Excellence in Autism.

Author information

Authors and Affiliations

  1. Department of Neurology, University of Utah, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT, 84132-2305, USA

    Nikki J. Kirkman, Jane E. Libbey, Thayne L. Sweeten, Edward K. Stevenson & Robert S. Fujinami

  2. Department of Psychiatry, University of Utah, 30 North 1900 East, 5R110 SOM, Salt Lake City, UT, 84132, USA

    Hilary H. Coon, Judith N. Miller, Janet E. Lainhart & William M. McMahon

Authors
  1. Nikki J. Kirkman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jane E. Libbey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thayne L. Sweeten
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hilary H. Coon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Judith N. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Edward K. Stevenson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Janet E. Lainhart
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. William M. McMahon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Robert S. Fujinami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert S. Fujinami.

Additional information

Nikki J. Kirkman and Jane E. Libbey contributed equally to this manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirkman, N.J., Libbey, J.E., Sweeten, T.L. et al. How Relevant are GFAP Autoantibodies in Autism and Tourette Syndrome?. J Autism Dev Disord 38, 333–341 (2008). https://doi.org/10.1007/s10803-007-0398-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-007-0398-9

Keywords

Search

Navigation