TY  - JOUR
AU  - Su, Julia
AU  - Gupta, Rohan
AU  - van Hoof, Scott
AU  - Kreye, Jakob
AU  - Prüß, Harald
AU  - Spielman, Benjamin
AU  - Brimberg, Lior
AU  - Volpe, Bruce T
AU  - Huerta, Patricio T
AU  - Diamond, Betty
TI  - Heterogeneity of anti-Caspr2 antibodies: specificity and pathogenicity.
JO  - Translational Psychiatry
VL  - 15
IS  - 1
SN  - 2158-3188
CY  - London
PB  - Nature Publishing Group
M1  - DZNE-2025-01319
SP  - 498
PY  - 2025
AB  - Maternal anti-Caspr2 (Contactin-associated protein-like 2) antibodies have been associated with increased risk for autism spectrum disorder (ASD). Previous studies have shown that in utero exposure to anti-Caspr2 antibodies results in a phenotype with ASD-like features in male mice. Here we ask whether four newly generated antibodies against Caspr2 are pathogenic to the developing fetal brain and whether they function through similar means. Our results show that these novel anti-Caspr2 antibodies recognize different epitopes of Caspr2. In utero exposure to these antibodies elicits differential behavioral phenotypes in male offspring, as demonstrated in the social interaction task, as well as phenotypic alterations in the open-field and light-dark tasks. These results demonstrate variability in the antigenic specificity and pathogenicity of anti-Caspr2 antibodies which may have clinical implications.
KW  - Animals
KW  - Nerve Tissue Proteins: immunology
KW  - Male
KW  - Female
KW  - Mice
KW  - Autism Spectrum Disorder: immunology
KW  - Membrane Proteins: immunology
KW  - Pregnancy
KW  - Autoantibodies: immunology
KW  - Prenatal Exposure Delayed Effects: immunology
KW  - Behavior, Animal
KW  - Brain: immunology
KW  - Brain: embryology
KW  - Humans
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
KW  - Autoantibodies (NLM Chemicals)
KW  - CNTNAP2 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41257955
C2  - pmc:PMC12644748
DO  - DOI:10.1038/s41398-025-03677-w
UR  - https://pub.dzne.de/record/282556
ER  -