Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism

Ann Clin Psychiatry. Jul-Sep 2009;21(3):148-61.

Abstract

Background: Autism causes incapacitating neurologic problems in children that last a lifetime. The author of this article previously hypothesized that autism may be caused by autoimmunity to the brain, possibly triggered by a viral infection. This article is a summary of laboratory findings to date plus new data in support of an autoimmune pathogenesis for autism.

Methods: Autoimmune markers were analyzed in the sera of autistic and normal children, but the cerebrospinal fluid (CSF) of some autistic children was also analyzed. Laboratory procedures included enzyme-linked immunosorbent assay and protein immunoblotting assay.

Results: Autoimmunity was demonstrated by the presence of brain autoantibodies, abnormal viral serology, brain and viral antibodies in CSF, a positive correlation between brain autoantibodies and viral serology, elevated levels of proinflammatory cytokines and acute-phase reactants, and a positive response to immunotherapy. Many autistic children harbored brain myelin basic protein autoantibodies and elevated levels of antibodies to measles virus and measles-mumps-rubella (MMR) vaccine. Measles might be etiologically linked to autism because measles and MMR antibodies (a viral marker) correlated positively to brain autoantibodies (an autoimmune marker)--salient features that characterize autoimmune pathology in autism. Autistic children also showed elevated levels of acute-phase reactants--a marker of systemic inflammation.

Conclusions: The scientific evidence is quite credible for our autoimmune hypothesis, leading to the identification of autoimmune autistic disorder (AAD) as a major subset of autism. AAD can be identified by immune tests to determine immune problems before administering immunotherapy. The author has advanced a speculative neuroautoimmune (NAI) model for autism, in which virus-induced autoimmunity is a key player. The latter should be targeted by immunotherapy to help children with autism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Viral / blood
  • Autistic Disorder / blood
  • Autistic Disorder / cerebrospinal fluid
  • Autistic Disorder / immunology*
  • Autoantibodies / immunology
  • Autoimmunity / immunology*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Brain / immunology
  • Child
  • Diphtheria-Tetanus Vaccine / blood
  • Diphtheria-Tetanus-Pertussis Vaccine / blood
  • Enzyme-Linked Immunosorbent Assay / methods
  • Hepatitis B Vaccines / blood
  • Humans
  • Immunoblotting / methods
  • Measles-Mumps-Rubella Vaccine / blood
  • Mercury / immunology
  • Phenotype*

Substances

  • Antibodies, Viral
  • Autoantibodies
  • Biomarkers
  • Diphtheria-Tetanus Vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Hepatitis B Vaccines
  • Measles-Mumps-Rubella Vaccine
  • Mercury