Skip to main content

Are there altered antibody responses to measles, mumps, or rubella viruses in autism?

Abstract

The role that virus infections play in autism is not known. Others have reported that antibodies against measles virus are higher in the sera/plasma of children with autism versus controls. The authors investigated antibody titers to measles, mumps, and rubella viruses and diphtheria toxoid in children with autism, both classic onset (33) and regressive onset (26) forms, controls (25, healthy age- and gender-matched) and individuals with Tourette’s syndrome (24) via enzyme-linked immunosorbent assays. No significant differences in antibody titers to measles, mumps, and rubella viruses and diphtheria toxoid were found among the four groups. Additionally, there were no significant differences between the four groups for total immunoglobulin (Ig)G or IgM. Interestingly, the authors did find a significant number (15/59) of autism subjects (classic and regressive onset combined) who had a very low or no antibody titer against rubella virus, compared to a combine control/Tourette’s group (2/49).

This is a preview of subscription content, access via your institution.

References

  • American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders, fourth edition, text revision. Washington, DC: American Psychiatric Association.

    Book  Google Scholar 

  • Asher DM (1991). Slow viral infections of the human nervous system. In Infections of the central nervous system. Scheld WM, Whitley RJ, Durack, DT (eds). New York: Raven Press, pp 145–166.

    Google Scholar 

  • 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. Psychol Med 25: 63–77.

    CAS  Article  PubMed  Google Scholar 

  • Bernard CC, Townsend E, Randell VB, Williamson HG (1983). Do antibodies to myelin basic protein isolated from multiple sclerosis cross-react with measles and other common virus antigens? Clin Exp Immunol 52: 98–106.

    CAS  PubMed  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. JAMA 285: 3093–3099.

    CAS  Article  PubMed  Google Scholar 

  • Chess S (1971). Autism in children with congenital rubella. J Autism Child Schizophr 1: 33–47.

    CAS  Article  PubMed  Google Scholar 

  • Chess S (1977). Follow-up report on autism in congenital rubella. J Autism Child Schizophr 7: 69–81.

    CAS  Article  PubMed  Google Scholar 

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

    Google Scholar 

  • Croonenberghs J, Wauters A, Devreese K, Verkerk R, Scharpe S, Bosmans E, Egyed B, Deboutte D, Maes M (2002). Increased serum albumin, gamma globulin, immunoglobulin IgG, and IgG2 and IgG4 in autism. Psychol Med 32: 1457–1463.

    CAS  Article  PubMed  Google Scholar 

  • Dales L, Hammer SJ, Smith NJ (2001). Time trends in autism and in MMR immunization coverage in California. JAMA 285: 1183–1185.

    CAS  Article  PubMed  Google Scholar 

  • Ferrari P, Marescot MR, Moulias R, Bursztejn C, Deville Chabrolle A, Thiollet M, Lesourd B, Braconnier A, Dreux C, Zarifian E, Fermanian J (1988). Immune status in infantile autism. Correlation between the immune status, autistic symptoms and levels of serotonin. Encephale 14: 339–344.

    CAS  PubMed  Google Scholar 

  • Fombonne E (2003). The prevalence of autism. JAMA 289: 87–89.

    Article  PubMed  Google Scholar 

  • Fombonne E, Chakrabarti S (2001). No evidence for a new variant of measles-mumps-rubella-induced autism. Pediatrics 108: E58.

    CAS  Article  PubMed  Google Scholar 

  • Fujinami RS, Oldstone MBA (1980). Alterations in expression of measles virus polypeptides by antibody: molecular events in antibody-induced antigenic modulation. J Immunol 125: 78–85.

    CAS  PubMed  Google Scholar 

  • Garg RK (2002). Subacute sclerosing panencephalitis. Postgrad Med J 78: 63–70.

    CAS  Article  PubMed  Google Scholar 

  • Gillberg C, Wing L (1999). Autism: not an extremely rare disorder. Acta Psychiatr Scand 99: 399–406.

    CAS  Article  PubMed  Google Scholar 

  • Goldberg WA, Osann K, Filipek PA, Laulhere T, Jarvis K, Modahl C, Flodman P, Spence MA (2003). Language and other regression: assessment and timing. J Autism Dev Disord 33: 607–616.

    Article  PubMed  Google Scholar 

  • Gupta S, Aggarwal S, Heads C (1996). Dysregulated immune system in children with autism: Beneficial effects of intravenous immune globulin on autistic characteristics. J Autism Dev Disord 26: 439–452.

    CAS  Article  PubMed  Google Scholar 

  • Jahnke U, Fischer EH, Alvord EC Jr (1985). Sequence homology between certain viral proteins and proteins related to encephalomyelitis and neuritis. Science 229: 282–284.

    CAS  Article  PubMed  Google Scholar 

  • Jankovic J (2001). Tourette’s syndrome. N Engl J Med 345: 1184–1192.

    CAS  Article  PubMed  Google Scholar 

  • Jansen VAA, Stollenwerk N, Jensen HJ, Ramsay ME, Edmunds WJ, Rhodes CJ (2003). Measles outbreaks in a population with declining vaccine uptake. Science 301: 804.

    CAS  Article  PubMed  Google Scholar 

  • Jingwu Z, Chin Y, Henderikx P, Medaer R, Chou C-HJ, Raus JC (1991). Antibodies to myelin basic protein and measles virus in multiple sclerosis: precursor frequency analysis of the antibody producing B cells. Autoimmunity 11: 27–34.

    CAS  Article  PubMed  Google Scholar 

  • Kawashima H, Mori T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A (2000). Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci 45: 723–729.

    CAS  Article  PubMed  Google Scholar 

  • Kaye JA, del Mar Melero-Montes M, Jick H (2001). Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ 322: 460–463.

    CAS  Article  PubMed  Google Scholar 

  • Kennedy RC, Byers VS, Marchalonis JJ (2004). Measles virus infection and vaccination: potential role in chronic illness and associated adverse events. Crit Rev Immunol 24: 129–156.

    CAS  Article  PubMed  Google Scholar 

  • Kiessling LS, Marcotte AC, Culpepper L (1993). Antineuronal antibodies in movement disorders. Pediatrics 92: 39–43.

    CAS  PubMed  Google Scholar 

  • King JC Jr, Lichenstein R, Feigelman S, Luna C, Permutt TJ, Patel J (1993). Measles, mumps, and rubella antibodies in vaccinated Baltimore children. Am J Dis Child 147: 558–560.

    PubMed  Google Scholar 

  • Kirkman NJ, Libbey JE, Sweeten TL, Coon HH, Miller JN, Stevenson EK, Lainhart JE, McMahon WM, Fujinami RS (2007). How relevant are GFAP autoantibodies in autism? J Autism Dev Disord, in press.

  • Libbey JE, Sweeten TL, McMahon WM, Fujinami RS (2005). Autistic disorder and viral infections. J NeuroVirol 11: 1–10.

    Article  PubMed  Google Scholar 

  • Libbey JE, Coon HH, Kirkman NJ, Sweeten TL, Miller JN, Stevenson EK, Lainhart JE, McMahon WM, Fujinami RS (2007). Are there enhanced MBP autoantibodies in autism? J Autism Dev Disord, in press.

  • Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, 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. J Autism Dev Disord 30: 205–223.

    CAS  Article  PubMed  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. J Autism Dev Disord 24: 659–685.

    CAS  Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, Olsen J, Melbye M (2002). A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med 347: 1477–1482.

    Article  PubMed  Google Scholar 

  • Madsen KM, Vestergaard M (2004). MMR vaccination and autism: what is the evidence for a causal association? Drug Saf 27: 831–840.

    Article  PubMed  Google Scholar 

  • Mäkelä A, Nuorti JP, Peltola H (2002). Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics 110: 957–963.

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Panitch HS, Hooper CJ, Johnson KP (1980). CSF antibody to myelin basic protein. Measurement in patients with multiple sclerosis and subacute sclerosing panencephalitis. Arch Neurol 37: 206–209.

    CAS  PubMed  Google Scholar 

  • Peltola H, Patja A, Leinikki P, Valle M, Davidkin I, Paunio M (1998). No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study. Lancet 351: 1327–1328.

    CAS  Article  PubMed  Google Scholar 

  • Peterson MR, Torrey EF (1976). Viruses and other infectious agents as behavioral teratogens. In The autistic syndromes. Coleman M (ed). New York: American Elsevier, pp 23–42.

    Google Scholar 

  • Plioplys AV (1998). Intravenous immunoglobulin treatment of children with autism. J Child Neurol 13: 79–82.

    CAS  Article  PubMed  Google Scholar 

  • Plioplys AV, Greaves A, Kazemi K, Silverman E (1994). Immunoglobin reactivity in autism and Rett’s syndrome. Dev Brain Dysfunct 7: 12–16.

    Google Scholar 

  • Rice GPA, Fujinami RS (1986). Measles virus. In Methods of enzymatic analysis. Bergmeyer HU (ed). Deerfield Beach, FL: VCH Publishers: Deerfield Beach, pp 370–383.

    Google Scholar 

  • Richler J, Luyster R, Risi S, Hsu W-L, Dawson G, Bernier R, Dunn M, Hepburn S, Hyman SL, McMahon WM, Goudie-Nice J, Minshew N, Rogers S, Sigman M, Spence MA, Goldberg WA, Tager-Flusberg H, Volkmar FR, Lord C (2006). Is there a ‘regressive phenotype’ of autism spectrum disorder associated with the measles-mumpsrubella vaccine? A CPEA study. J Autism Dev Disord 36: 299–316.

    Article  PubMed  Google Scholar 

  • Rubio N, Cuesta A (1989). Lack of cross-reaction between myelin basic proteins and putative demyelinating virus envelope proteins. Mol Immunol 26: 663–668.

    CAS  Article  PubMed  Google Scholar 

  • Schotte A, Janssen PF, Megens AA, Leysen JE (1993). Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography. Brain Res 631: 191–202.

    CAS  Article  PubMed  Google Scholar 

  • Singh VK, Jensen RL (2003). Elevated levels of measles antibodies in children with autism. Pediatr Neurol 28: 292–294.

    Article  PubMed  Google Scholar 

  • Singh VK, Lin SX, Newell E, Nelson C (2002). Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism. J Biomed Sci 9: 359–364.

    CAS  Article  PubMed  Google Scholar 

  • Singh VK, Lin SX, Yang VC (1998). Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. Clin Immunol Immunopathol 89: 105–108.

    CAS  Article  PubMed  Google Scholar 

  • Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG, Hall AJ (2004). MMR vaccination and pervasive developmental disorders: a case-control study. Lancet 364: 963–969.

    Article  PubMed  Google Scholar 

  • Stubbs EG (1976). Autistic children exhibit undetectable hemagglutination-inhibition antibody titers despite previous rubella vaccination. J Autism Child Schizophr 6: 269–274.

    CAS  Article  PubMed  Google Scholar 

  • Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK (1998). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 155: 264–271.

    CAS  PubMed  Google Scholar 

  • Sweeten TL, Fujinami RS (2004). A potential link between measles virus and autism: age-matched control groups are essential. Pediatr Neurol 30: 78.

    Article  PubMed  Google Scholar 

  • Taylor B, Miller E, Farrington CP, Petropoulos MC, Favot-Mayaud I, Li J, Waight PA (1999). Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 353: 2026–2029.

    CAS  Article  PubMed  Google Scholar 

  • Taylor B, Miller E, Lingam R, Andrews N, Simmons A, Stowe J (2002). Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study. BMJ 324: 393–396.

    Article  PubMed  Google Scholar 

  • Thomas DRH, Salmon RL, King J (1998). Rates of first measles-mumps-rubella immunisation in Wales (UK). Lancet 351: 1927.

    CAS  Article  PubMed  Google Scholar 

  • Tookey P (2004). Rubella in England, Scotland and Wales. Euro Surveill 9: 21–23.

    CAS  PubMed  Google Scholar 

  • Trajkovski V, Ajdinski L, Spiroski M (2004). Plasma concentration of immunoglobulin classes and subclasses in children with autism in the Republic of Macedonia: retrospective study. Croat Med J 45: 746–749.

    PubMed  Google Scholar 

  • Uhlmann V, Martin CM, Sheils O, Pilkington L, Silva I, Killalea A, Murch SB, Wakefield AJ, O’Leary JJ (2002). Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Mol Pathol 55: 84–90.

    CAS  Article  PubMed  Google Scholar 

  • Wakefield AJ, Ashwood P, Limb K, Anthony A (2005). The significance of ileo-colonic lymphoid nodular hyperplasia in children with autistic spectrum disorder. Eur J Gastroenterol Hepatol 17: 827–836.

    Article  PubMed  Google Scholar 

  • Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA (1998). Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children. Lancet 351: 637–641.

    CAS  Article  PubMed  Google Scholar 

  • Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle C, Murphy C (2003). Prevalence of autism in a US metropolitan area. JAMA 289: 49–55.

    Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  • Zimmerman AW, Potter NT, Stakkestad A, Frye VH (1995). Serum immunoglobulins and autoimmune profiles in children with autism. Ann Neurol 38: 528.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert S. Fujinami.

Additional information

This work was supported by NIH U19 HD/DC35476, which is part of the NICHD/NIDCD Collaborative Programs for Excellence in Autism.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Libbey, J.E., Coon, H.H., Kirkman, N.J. et al. Are there altered antibody responses to measles, mumps, or rubella viruses in autism?. Journal of NeuroVirology 13, 252–259 (2007). https://doi.org/10.1080/13550280701278462

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280701278462

Keywords

  • autism
  • immunoglobulin
  • Tourette’s syndrome