Neuroglial activation and neuroinflammation in the brain of patients with autism

Authors

  • Diana L. Vargas MD,

    1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
    2. Division of Neuroimmunology and Infectious Disorders, Johns Hopkins University School of Medicine, Baltimore, MD
    Search for more papers by this author
  • Caterina Nascimbene MD,

    1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
    2. Division of Neuroimmunology and Infectious Disorders, Johns Hopkins University School of Medicine, Baltimore, MD
    3. Department of Neurology, University of Milan, Italy
    Search for more papers by this author
  • Chitra Krishnan MHS,

    1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
    Search for more papers by this author
  • Andrew W. Zimmerman MD,

    1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
    2. Kennedy Krieger Institute
    Search for more papers by this author
  • Carlos A. Pardo MD

    Corresponding author
    1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
    2. Division of Neuroimmunology and Infectious Disorders, Johns Hopkins University School of Medicine, Baltimore, MD
    3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
    • Department of Neurology, Johns Hopkins University School of Medicine, Pathology 627, 600 North Wolfe Street, Baltimore, MD 21287
    Search for more papers by this author

Abstract

Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh-frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)–1 and tumor growth factor–β1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain. Ann Neurol 2005

An Erratum has been published for this article in Ann Neurol 57: 304, 2005.

Ancillary