Autism-specific maternal autoantibodies recognize critical proteins in developing brain

Transl Psychiatry. 2013 Jul 9;3(7):e277. doi: 10.1038/tp.2013.50.

Abstract

Autism spectrum disorders (ASDs) are neurodevelopmental in origin, affecting an estimated 1 in 88 children in the United States. We previously described ASD-specific maternal autoantibodies that recognize fetal brain antigens. Herein, we demonstrate that lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2) and Y-box-binding protein to comprise the seven primary antigens of maternal autoantibody-related (MAR) autism. Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of ASD children and only 1% of controls. ASD children from mothers with specific reactivity to LDH, STIP1 and CRMP1 and/or cypin (7% vs 0% in controls; P<0.0002; odds ratios of 24.2 (95% confidence interval: 1.45-405)) had elevated stereotypical behaviors compared with ASD children from mothers lacking these antibodies. We describe the first panel of clinically significant biomarkers with over 99% specificity for autism risk thereby advancing our understanding of the etiologic mechanisms and therapeutic possibilities for MAR autism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibody Specificity / immunology
  • Autistic Disorder / immunology*
  • Autoantibodies / immunology*
  • Blotting, Western
  • Brain / growth & development*
  • Brain / immunology
  • Child
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Guanine Deaminase / immunology
  • Humans
  • Intercellular Signaling Peptides and Proteins / immunology
  • Isoenzymes / immunology
  • L-Lactate Dehydrogenase / immunology
  • Lactate Dehydrogenase 5
  • Maternal-Fetal Exchange / immunology
  • Nerve Tissue Proteins / immunology*
  • Pregnancy
  • Stereotyped Behavior
  • Y-Box-Binding Protein 1 / immunology

Substances

  • Autoantibodies
  • CRMP1 protein, human
  • GDA protein, human
  • Intercellular Signaling Peptides and Proteins
  • Isoenzymes
  • Nerve Tissue Proteins
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • collapsin response mediator protein-2
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • lactate dehydrogenase 1
  • Guanine Deaminase