JHU- Maternal antibodies study

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Fri Oct 6, 2006 4:57 pm (PST)

Brain, Behavior, and Immunity

Article in Press, Corrected Proof - Note to users

doi:10.1016/

j.bbi.2006.08.005

Copyright © 2006 Elsevier Inc. All rights reserved.

Maternal antibrain antibodies in autism

W. Zimmermana, b, d, , , L. Connorsa, Karla J. Mattesonb,

Li-Ching Leec, Harvey S. Singerd, n A. Castanedae and A.

Pearcee, f, g

aDepartment of Neurology and Developmental Medicine, Kennedy Krieger

Institute, 707 North Broadway, Baltimore, MD 21205, USA

bDevelopmental and Genetic Center, University of Tennessee Medical

Center, Knoxville, TN, USA

cCenter for Autism and Developmental Disabilities Epidemiology, s

Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

dDepartment of Neurology, s Hopkins University School of Medicine,

Baltimore, MD, USA

eCenter for Aging and Developmental Biology, Aab Institute of Biomedical

Science, Rochester, NY, USA

fDepartment of Biochemistry and Biophysics, University of Rochester

School of Medicine and Dentistry, Rochester, NY, USA

gDepartment of Neurology, University of Rochester School of Medicine and

Dentistry, Rochester, NY, USA

Received 5 May 2006; revised 4 August 2006; accepted 16 August 2006.

Available online 6 October 2006.

Abstract

Autism is a neurodevelopmental disorder of prenatal onset that is

behaviorally defined. There is increasing evidence for systemic and

neuroimmune mechanisms in children with autism. Although genetic factors

are important, atypical prenatal maternal immune responses may also be

linked to the pathogenesis of autism. We tested serum reactivity in 11

mothers and their autistic children, maternal controls, and several

groups of control children, to prenatal, postnatal, and adult rat brain

proteins, by immunoblotting. Similar patterns of reactivity to prenatal

(gestational day 18), but not postnatal (day 8) or adult rat brain

proteins were identified in autistic children, their mothers, and

children with other neurodevelopmental disorders, and differed from

mothers of normal children, normal siblings of children with autism and

normal child controls. Specific patterns of antibody reactivity were

present in sera from the autism mothers, from 2 to 18 years after the

birth of their affected children and were unrelated to birth order.

Immunoblotting using specific antigens for myelin basic protein (MBP)

and glial acidic fibrillary protein (GFAP) suggests that these proteins

were not targets of the maternal antibodies. The identification of

specific serum antibodies in mothers of children with autism that

recognize prenatally expressed brain antigens suggests that these

autoantibodies could cross the placenta and alter fetal brain development.

Keywords: Autism; Maternal; Antibodies; Autoimmunity; Prenatal

Supported by the Jonty Foundation, the Autism Society of America, East

Tennessee Chapter, and NIH Grant T32 ES07026-27.