Heterogeneity of anti-Caspr2 antibodies: specificity and pathogenicity.

Researchers studied antibodies that may contribute to autism risk during pregnancy. They found that different types of these antibodies affect developing brains differently in mice. Male mouse babies showed various behavioral changes depending on which antibody they were exposed to before birth. This suggests that not all of these antibodies work the same way, which might explain why autism presents differently in different children.

This preclinical study investigated four newly generated anti-Caspr2 antibodies and their effects on fetal brain development in mice. Previous research linked maternal anti-Caspr2 antibodies to increased autism spectrum disorder risk. The study found that these novel antibodies recognize different parts of the Caspr2 protein and produce varying behavioral outcomes in male mouse offspring when exposed during pregnancy. Behavioral differences were observed in social interaction, open-field exploration, and light-dark preference tasks.

The findings suggest that anti-Caspr2 antibodies vary in their antigenic specificity and ability to cause developmental changes, which may help explain clinical variability in autism presentations.

Findings suggest maternal anti-Caspr2 antibodies may contribute to autism heterogeneity through different mechanisms. This could inform future development of antibody-specific screening approaches and targeted interventions. However, translation from mouse models to human clinical applications requires validation studies.

Study conducted in mice only, limiting direct clinical translation. Sample size not reported. Behavioral assessments limited to specific tasks. Long-term developmental outcomes not assessed. Female offspring effects not clearly reported.

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.