MATERNAL AUTOANTIBODIES AS A POSSIBLE ASD-RISK BIOMARKER

Abstract

Abstract Maternal autoantibody-related ASD (MAR ASD) is a subtype of autism in which pathogenic maternal autoantibodies (IgG) can cross the placenta, access the developing brain, and cause neurodevelopmental alterations and behaviors associated with autism in the exposed offspring. We previously reported maternal IgG response to eight proteins (CRMP1, CRMP2, GDA LDHA, LDHB, NSE, STIP1, and YBOX) and that reactivity two or more specific proteins (MAR ASD patterns) can be used to predict ASD risk in a discovery study. Objective In the current study, we aimed to validate the previously described MAR ASD patterns (CRMP1+GDA, CRMP1+CRMP2, NSE+STIP1, CRMP2+STIP1, LDHA+YBOX, LDHB+YBOX, GDA+YBOX, STIP1+YBOX, and CRMP1+STIP1) and their accuracy to predict ASD risk in a prospective cohort. Methods We used plasma from mothers of autistic children (ASD= 540) and general population controls (not verified as typically developing) (GP=420) collected by the Early Markers of Autism (EMA) study. We evaluated maternal IgG reactivity against each of the eight fetal brain proteins by ELISA and used Fisher Exact Test (p < 0.05) to compare the association for each pattern with child outcome (ASD vs GP). Results We found reactivity to at least one protein in more than 50% of the samples in the case and control groups, suggesting that reactivity to a single antigen is not diagnosis-specific. However, when we tested the nine previously identified MAR ASD patterns, we found highly-specific reactivity in 10% ASD group vs 1% of the GP controls and increased the odds for an ASD outcome nearly 8-fold (p< 0.001, OR 7.81, 95% CI from 3.32 to 22.43) demonstrating that the MAR ASD patterns are highly specific for the case group and could be used to assess ASD risk prior to symptoms. Supported by EPA2P01ES011269-11, 83543201, R01ES015359, NICHD funded IDDRC P50 (P50HD103526), CONACYT-UC MEXUS Doctoral Fellowships 2015.