title: Autism-specific maternal autoantibodies recognize critical proteins in developing brain.
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.
authors.affiliation: Department of Internal Medicine, University of California at Davis, Davis, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Braunschweig
authors.forename: P
authors.initials: P
authors.lastname: Krakowiak
authors.forename: P
authors.initials: P
authors.lastname: Duncanson
authors.forename: R
authors.initials: R
authors.lastname: Boyce
authors.forename: R L
authors.initials: RL
authors.lastname: Hansen
authors.forename: P
authors.initials: P
authors.lastname: Ashwood
authors.forename: I
authors.initials: I
authors.lastname: Hertz-Picciotto
authors.forename: I N
authors.initials: IN
authors.lastname: Pessah
authors.forename: J
authors.initials: J
authors.lastname: Van de Water
mesh_terms: D000918:Antibody Specificity / Q000276:immunology; D001321:Autistic Disorder / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development* / Q000276:immunology; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006148:Guanine Deaminase / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology; D007770:L-Lactate Dehydrogenase / Q000276:immunology; D000080864:Lactate Dehydrogenase 5; D008431:Maternal-Fetal Exchange / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D011247:Pregnancy; D013239:Stereotyped Behavior; D051840:Y-Box-Binding Protein 1 / Q000276:immunology; D000098855:Collapsin Response Mediator Protein 1
chemical_list: D001323:Autoantibodies; D006148:Guanine Deaminase; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D009419:Nerve Tissue Proteins; D051840:Y-Box-Binding Protein 1; C102924:CRMP1 protein, human; D000098855:Collapsin Response Mediator Protein 1; C402297:GDA protein, human; C070856:YBX1 protein, human; C095114:collapsin response mediator protein-2; C409667:lactate dehydrogenase 1