biostudies-literatureSu JDeutsche Forschungsgemeinschaft (German Research Foundation)NIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)498https://www.ebi.ac.uk/biostudies/studies/S-EPMC12644748biostudies-literatureUnknown15(1)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 variabilitTranslational psychiatryHeterogeneity of anti-Caspr2 antibodies: specificity and pathogenicity.PMC126447485P01AI073693FOR3004 (project number 415914819).P01 AI073693FOR3004 project number 415914819Gupta RBrimberg Lvan Hoof SSpielman BDiamond BPruß HVolpe BTKreye JHuerta PTSu JfalseHeterogeneity of anti-Caspr2 antibodies: specificity and pathogenicity.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 variabilit2025-01-01T00:00:00Z2025 Nov2026-06-05T19:15:45.407Z2026-05-20T03:14:20.802ZS-EPMC126447484125795510.1038/s41398-025-03677-w