PT  - JOURNAL ARTICLE
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
AID  - 10.1101/2025.01.16.633238
DP  - 2025 Jan 01
TA  - bioRxiv
PG  - 2025.01.16.633238
4099  - http://biorxiv.org/content/early/2025/01/21/2025.01.16.633238.short
4100  - http://biorxiv.org/content/early/2025/01/21/2025.01.16.633238.full
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 the novel anti-Caspr2 antibodies recognize different epitopes of Caspr2. In utero exposure to these antibodies elicits differential ASD-like phenotypes in male offspring, tested in the social interaction, 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.Competing Interest StatementThe authors have declared no competing interest.