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2016 ; 21
(12
): 1663-1671
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Caspr2-reactive antibody cloned from a mother of an ASD child mediates an
ASD-like phenotype in mice
#MMPMID27698429
Brimberg L
; Mader S
; Jeganathan V
; Berlin R
; Coleman TR
; Gregersen PK
; Huerta PT
; Volpe BT
; Diamond B
Mol Psychiatry
2016[Dec]; 21
(12
): 1663-1671
PMID27698429
show ga
Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting
males. It encompasses a group of neurodevelopmental abnormalities characterized
by impaired social interaction and communication, stereotypic behaviors and motor
dysfunction. Although recent advances implicate maternal brain-reactive
antibodies in a causative role in ASD, a definitive assessment of their
pathogenic potential requires cloning of such antibodies. Here, we describe the
isolation and characterization of monoclonal brain-reactive antibodies from blood
of women with brain-reactive serology and a child with ASD. We further
demonstrate that male but not female mice exposed in utero to the C6 monoclonal
antibody, binding to contactin-associated protein-like 2 (Caspr2), display
abnormal cortical development, decreased dendritic complexity of excitatory
neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as
impairments in sociability, flexible learning and repetitive behavior.
Anti-Caspr2 antibodies are frequent in women with brain-reactive serology and a
child with ASD. Together these studies provide a methodology for obtaining
monclonal brain-reactive antibodies from blood B cells, demonstrate that ASD can
result from in utero exposure to maternal brain-reactive antibodies of single
specificity and point toward the exciting possibility of prognostic and
protective strategies.