Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A

J Neuroimmunol. 2002 Aug;129(1-2):168-77. doi: 10.1016/s0165-5728(02)00180-7.

Abstract

We measured autoantibodies against nine different neuron-specific antigens and three cross-reactive peptides in the sera of autistic subjects and healthy controls by means of enzyme-linked immunosorbent assay (ELISA) testing. The antigens were myelin basic protein (MBP), myelin-associated glycoprotein (MAG), ganglioside (GM1), sulfatide (SULF), chondroitin sulfate (CONSO4), myelin oligodendrocyte glycoprotein (MOG), alpha,beta-crystallin (alpha,beta-CRYS), neurofilament proteins (NAFP), tubulin and three cross-reactive peptides, Chlamydia pneumoniae (CPP), streptococcal M protein (STM6P) and milk butyrophilin (BTN). Autistic children showed the highest levels of IgG, IgM and IgA antibodies against all neurologic antigens as well as the three cross-reactive peptides. These antibodies are specific because immune absorption demonstrated that only neuron-specific antigens or their cross-reactive epitopes could significantly reduce antibody levels. These antibodies may have been synthesized as a result of an alteration in the blood-brain barrier. This barrier promotes access of preexisting T-cells and central nervous system antigens to immunocompetent cells, which may start a vicious cycle. These results suggest a mechanism by which bacterial infections and milk antigens may modulate autoimmune responses in autism.

MeSH terms

  • Antigens / immunology*
  • Antigens, Bacterial / immunology*
  • Autistic Disorder / blood
  • Autistic Disorder / immunology*
  • Autistic Disorder / physiopathology
  • Autoimmune Diseases of the Nervous System / blood
  • Autoimmune Diseases of the Nervous System / immunology*
  • Autoimmune Diseases of the Nervous System / physiopathology
  • Bacterial Infections / blood
  • Bacterial Infections / complications*
  • Bacterial Infections / immunology
  • Bacterial Outer Membrane Proteins / immunology
  • Butyrophilins
  • Carrier Proteins / immunology
  • Child
  • Child, Preschool
  • Chlamydophila pneumoniae / immunology
  • Cross Reactions / immunology
  • Encephalitis / immunology
  • Encephalitis / physiopathology
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Male
  • Membrane Glycoproteins / immunology
  • Milk Hypersensitivity / blood
  • Milk Hypersensitivity / complications*
  • Milk Hypersensitivity / immunology
  • Myelin Basic Protein / immunology
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein
  • Neurons / immunology
  • Neurotoxins / immunology
  • Streptococcus / immunology

Substances

  • Antigens
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Butyrophilins
  • Carrier Proteins
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • MOG protein, human
  • Membrane Glycoproteins
  • Myelin Basic Protein
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Neurotoxins
  • streptococcal M protein