Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders

doi:10.1016/S0022-3476(99)70248-9

The Journal of Pediatrics

Volume 134, Issue 5, May 1999, Pages 607-613

Presented in part at the Child Neurology Society meeting, Phoenix, Arizona, October 29-November 3, 1997.

https://doi.org/10.1016/S0022-3476(99)70248-9 Get rights and content

Abstract

Objective: Etiologically unexplained disorders of language and social development have often been reported to improve in patients treated with immune-modulating regimens. Here we determined the frequency of autoantibodies to brain among such children. Design: We collected sera from a cohort of children with (1) pure Landau-Kleffner syndrome (n = 2), (2) Landau-Kleffner syndrome variant (LKSV, n = 11), and (3) autistic spectrum disorder (ASD, n = 11). None had received immune-modulating treatment before the serum sample was obtained. Control sera (n = 71) were from 29 healthy children, 22 with non-neurologic illnesses (NNIs), and 20 children with other neurologic disorders (ONDs). We identified brain autoantibodies by immunostaining of human temporal cortex and antinuclear autoantibodies using commercially available kits. Results: IgG anti-brain autoantibodies were present in 45% of sera from children with LKSV, 27% with ASD, and 10% with ONDs compared with 2% from healthy children and control children with NNIs. IgM autoantibodies were present in 36% of sera from children with ASD, 9% with LKSV, and 15% with ONDs compared with 0% of control sera. Labeling studies identified one antigenic target to be endothelial cells. Antinuclear antibodies with titers ≥1:80 were more common in children with ASD and control children with ONDs. Conclusion: Children with LKSV and ASD have a greater frequency of serum antibodies to brain endothelial cells and to nuclei than children with NNIs or healthy children. The presence of these antibodies raises the possibility that autoimmunity plays a role in the pathogenesis of language and social developmental abnormalities in a subset of children with these disorders. (J Pediatr 1999;134:607-13)

Section snippets

METHODS

Informed consent for a blood sample was obtained from parents of children presenting with severe communication disorders coupled with seizures and mild to severe social skills abnormalities. Whole blood was drawn and centrifuged. The serum was decanted and frozen until assay.

Clinical Features (Tables II-VI)

After chart review by blinded observers (S.A. and R.K.D.), 24 children who presented with language and communication disorders coupled with seizures or EEG abnormalities and/or social skills deficits were classified as having LKS (n = 2), LKSV (n = 11), and ASD (n = 11). A few clinical seizures occurred in both patients with LKS. Although all 11 patients with LKSV had moderate to severe epileptiform abnormalities on EEGs, only one had seizures. None of the children with ASD had seizures,

DISCUSSION

Previous studies show various abnormal immune responses in children with autism or LKS. For example, a proportion of patients with ASD have T-cell dysfunction or abnormal numbers of T cells.10, 12, 14, 16, 19 LKS has been associated with infections or postinfectious processes in several patients.40, 43 Central nervous system targets of autoantibodies, including myelin basic protein⁹ and neurofilament protein,¹⁹ have been identified in autistic patients. However, these autoantibodies are not

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^☆: Supported by National Institutes of Health grant 1 K08 NS01648-01 and by a grant from the Cure Autism Now Foundation.

^☆☆: Reprint requests: Anne M. Connolly, MD, Department of Neurology, Box 8111, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110.

^★: 0022-3476/99/$8.00 + 0 9/21/97330

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Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders☆,☆☆,★

Abstract

Section snippets

METHODS

Clinical Features (Tables II-VI)

DISCUSSION

Brain Behav Immun

J Neuroimmunol

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

J Neuroimmunol

Biol Psychol

J Neuroimmunol

Brain Dev

Pediatr Neurol

Brain Dev

The neuropsychology of autism

Brain

Disorders usually diagnosed in infancy, childhood or adolescence

Genetic influences and infantile autism

Nature

A full genome screen for autism with evidence for linkage to a region on chromosome 7q

Hum Mol Genet

Autism spectrum disorders in children with physical or mental disability or both. I. Clinical and epidemiological aspects

Dev Med Child Neurol

Acquired reversible autistic syndrome in acute encephalopathic illness in children

Arch Neurol

Brief report: dysregulated immune system in children with autism: beneficial effects of intravenous immune globulin on autistic characteristics

J Autism Dev Disord

Depressed lymphocyte responsiveness in autistic children

J Autism Child Schizophr

Immune abnormalities in patients with autism

J Autism Dev Disord

Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in autism

Immunol Invest