Heterogeneity 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 variability in the antigenic specificity and pathogenicity of anti-Caspr2 antibodies which may have clinical implications.

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Publication Details

Journal
Translational Psychiatry
Published
2025-11-15
DOI
https://doi.org/10.1038/s41398-025-03677-w
Citations
2
Primary Topic
Autism Spectrum Disorder Research
Type
article
Field-Weighted Citation Impact
2.86

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article

Heterogeneity of anti-Caspr2 antibodies: specificity and pathogenicity

Rohan Gupta, Patricio T. Huerta, Jakob Kreye, Scott van Hoof et al.
2 citations
Translational Psychiatry
Autism Spectrum Disorder Research
2.86
article

Heterogeneity of anti-Caspr2 antibodies: specificity and pathogenicity

Rohan Gupta, Patricio T. Huerta, Jakob Kreye, Scott van Hoof, Harald Prüß, Bruce T. Volpe, Benjamin Spielman, Lior Brimberg, Julia Su, Betty Diamond
article en
2 citations

Abstract

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.

Translational PsychiatryVol. 15(1)
Northwell Health (US), Feinstein Institute for Medical Research (US), Hofstra University (US), German Center for Neurodegenerative Diseases (DE), Humboldt-Universität zu Berlin (DE), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE)
U.S. Department of Defense, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Berlin Institute of Health, National Institutes of Health
Openalex Percentile: Top 8%
Autism Spectrum Disorder Research
2.86
DOIOpen Access PDFOpenAlex
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