title: Blocking and Binding Folate Receptor Alpha Autoantibodies Identify Novel Autism Spectrum Disorder Subgroups.
abstract: Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). They disrupt the transportation of folate across the blood-brain barrier by binding to the FRα. Children with ASD and FRAAs have been reported to respond well to treatment with a form of folate known as folinic acid, suggesting that they may be an important ASD subgroup to identify and treat. There has been no investigation of whether they manifest unique behavioral and physiological characteristics. Thus, in this study we measured both blocking and binding FRAAs, physiological measurements including indices of redox and methylation metabolism and inflammation as well as serum folate and B12 concentrations and measurements of development and behavior in 94 children with ASD. Children positive for the binding FRAA were found to have higher serum B12 levels as compared to those negative for binding FRAAs while children positive for the blocking FRAA were found to have relatively better redox metabolism and inflammation markers as compared to those negative for blocking FRAAs. In addition, ASD children positive for the blocking FRAA demonstrated better communication on the Vineland Adaptive Behavior Scale, stereotyped behavior on the Aberrant Behavioral Checklist and mannerisms on the Social Responsiveness Scale. This study suggests that FRAAs are associated with specific physiological and behavioral characteristics in children with ASD and provides support for the notion that these biomarkers may be useful for subgrouping children with ASD, especially with respect to targeted treatments.
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Frye
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: Leanna
authors.initials: L
authors.lastname: Delhey
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: John
authors.initials: J
authors.lastname: Slattery
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Tippett
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wynne
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Rose
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Kahler
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: Sirish C
authors.initials: SC
authors.lastname: Bennuri
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences Little Rock, AR, USA.
authors.forename: Stepan
authors.initials: S
authors.lastname: Melnyk
authors.affiliation: Department of Medicine, State University of New York-Downstate Medical Center Brooklyn, NY, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Sequeira
authors.affiliation: Department of Medicine, State University of New York-Downstate Medical Center Brooklyn, NY, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Quadros
keywords: autism spectrum disorders; folate receptor autoantibody; folinic acid; glutathione; redox metabolism