AUTHOR=Mazón-Cabrera Rut , Liesenborgs Jori , Brône Bert , Vandormael Patrick , Somers Veerle 

TITLE=Novel maternal autoantibodies in autism spectrum disorder: Implications for screening and diagnosis

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1067833

DOI=10.3389/fnins.2023.1067833

ISSN=1662-453X

ABSTRACT=Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which early recognition is a major challenge. Autoantibodies against fetal brain antigens have been found in the blood of mothers of children with ASD (m-ASD) and can be transferred to the fetus where they can impact neurodevelopment by binding to fetal brain proteins. This study aims to identify novel maternal autoantibodies reactive against human fetal brain antigens, and explore their use as biomarkers for ASD screening and diagnosis. A custom-made human fetal brain cDNA phage display library was constructed, and screened for antibody reactivity in m-ASD samples from the Simons Simplex collection (SSC) of the Simons Foundation Autism Research Initiative (SFARI), resulting in the identification of 6 novel University Hasselt (UH)-ASD antigens. These included three novel m-ASD autoantigens, i.e. ribosomal protein L23 (RPL23), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and calmodulin-regulated spectrin-associated protein 3 (CAMSAP3). Antibody reactivity against the 6 identified UH-ASD antigens was determined in plasma samples of 238 m-ASD and 90 mothers with typically developing children (m-TD). Antibody reactivity against a panel of four of these targets was found in 16% of m-ASD samples, compared to 4% in m-TD samples (p=0.0049). In several diagnostic scenarios, where screening and diagnostic instruments were applied in at-risk populations, the additional inclusion of antibody reactivity against one of these 4 targets could strongly increase the post-test probability for ASD. Maternal antibodies against 4 UH-ASD antigens could therefore provide a novel tool to support the diagnosis of ASD in a subset of individuals.