Frontiers in Immunology (Jan 2023)
Maternal synapsin autoantibodies are associated with neurodevelopmental delay
- Isabel Bünger,
- Isabel Bünger,
- Konstantin L. Makridis,
- Konstantin L. Makridis,
- Konstantin L. Makridis,
- Konstantin L. Makridis,
- Jakob Kreye,
- Jakob Kreye,
- Jakob Kreye,
- Jakob Kreye,
- Jakob Kreye,
- Jakob Kreye,
- Marc Nikolaus,
- Marc Nikolaus,
- Marc Nikolaus,
- Marc Nikolaus,
- Eva Sedlin,
- Eva Sedlin,
- Tim Ullrich,
- Tim Ullrich,
- Christian Hoffmann,
- Johannes Vincent Tromm,
- Helle Foverskov Rasmussen,
- Helle Foverskov Rasmussen,
- Dragomir Milovanovic,
- Markus Höltje,
- Harald Prüss,
- Harald Prüss,
- Angela M. Kaindl,
- Angela M. Kaindl,
- Angela M. Kaindl,
- Angela M. Kaindl
Affiliations
- Isabel Bünger
- Charité – Universitätsmedizin Berlin, Department of Neurology and Experimental Neurology, Berlin, Germany
- Isabel Bünger
- German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
- Konstantin L. Makridis
- Charité – Universitätsmedizin Berlin, Department of Pediatric Neurology, Berlin, Germany
- Konstantin L. Makridis
- Charité – Universitätsmedizin Berlin, Center for Chronically Sick Children, Berlin, Germany
- Konstantin L. Makridis
- Charité – Universitätsmedizin Berlin, German Epilepsy Center for Children and Adolescents, Berlin, Germany
- Konstantin L. Makridis
- Charité – Universitätsmedizin Berlin, Institute of Cell- and Neurobiology, Berlin, Germany
- Jakob Kreye
- Charité – Universitätsmedizin Berlin, Department of Neurology and Experimental Neurology, Berlin, Germany
- Jakob Kreye
- German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
- Jakob Kreye
- Charité – Universitätsmedizin Berlin, Department of Pediatric Neurology, Berlin, Germany
- Jakob Kreye
- Charité – Universitätsmedizin Berlin, Center for Chronically Sick Children, Berlin, Germany
- Jakob Kreye
- Charité – Universitätsmedizin Berlin, German Epilepsy Center for Children and Adolescents, Berlin, Germany
- Jakob Kreye
- Berlin Institute of Health (BIH), Berlin, Germany
- Marc Nikolaus
- Charité – Universitätsmedizin Berlin, Department of Pediatric Neurology, Berlin, Germany
- Marc Nikolaus
- Charité – Universitätsmedizin Berlin, Center for Chronically Sick Children, Berlin, Germany
- Marc Nikolaus
- Charité – Universitätsmedizin Berlin, German Epilepsy Center for Children and Adolescents, Berlin, Germany
- Marc Nikolaus
- Berlin Institute of Health (BIH), Berlin, Germany
- Eva Sedlin
- Charité – Universitätsmedizin Berlin, Department of Pediatric Neurology, Berlin, Germany
- Eva Sedlin
- Charité – Universitätsmedizin Berlin, Center for Chronically Sick Children, Berlin, Germany
- Tim Ullrich
- Charité – Universitätsmedizin Berlin, Department of Pediatric Neurology, Berlin, Germany
- Tim Ullrich
- Charité – Universitätsmedizin Berlin, Center for Chronically Sick Children, Berlin, Germany
- Christian Hoffmann
- German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
- Johannes Vincent Tromm
- German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
- Helle Foverskov Rasmussen
- Charité – Universitätsmedizin Berlin, Department of Neurology and Experimental Neurology, Berlin, Germany
- Helle Foverskov Rasmussen
- German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
- Dragomir Milovanovic
- German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
- Markus Höltje
- Charité - Universitätsmedizin Berlin, Institute of Integrative Neuroanatomy, Berlin, Germany
- Harald Prüss
- Charité – Universitätsmedizin Berlin, Department of Neurology and Experimental Neurology, Berlin, Germany
- Harald Prüss
- German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany
- Angela M. Kaindl
- Charité – Universitätsmedizin Berlin, Department of Pediatric Neurology, Berlin, Germany
- Angela M. Kaindl
- Charité – Universitätsmedizin Berlin, Center for Chronically Sick Children, Berlin, Germany
- Angela M. Kaindl
- Charité – Universitätsmedizin Berlin, German Epilepsy Center for Children and Adolescents, Berlin, Germany
- Angela M. Kaindl
- Charité – Universitätsmedizin Berlin, Institute of Cell- and Neurobiology, Berlin, Germany
- DOI
- https://doi.org/10.3389/fimmu.2023.1101087
- Journal volume & issue
-
Vol. 14
Abstract
Maternal autoantibodies can be transmitted diaplacentally, with potentially deleterious effects on neurodevelopment. Synapsin 1 (SYN1) is a neuronal protein that is important for synaptic communication and neuronal plasticity. While monoallelic loss of function (LoF) variants in the SYN1 gene result in X-linked intellectual disability (ID), learning disabilities, epilepsy, behavioral problems, and macrocephaly, the effect of SYN1 autoantibodies on neurodevelopment remains unclear. We recruited a clinical cohort of 208 mothers and their children with neurologic abnormalities and analyzed the role of maternal SYN1 autoantibodies. We identified seropositivity in 9.6% of mothers, and seropositivity was associated with an increased risk for ID and behavioral problems. Furthermore, children more frequently had epilepsy, macrocephaly, and developmental delay, in line with the SYN1 LoF phenotype. Whether SYN1 autoantibodies have a direct pathogenic effect on neurodevelopment or serve as biomarkers requires functional experiments.
Keywords
- synapsin 1
- antineuronal autoantibodies
- transplacental transfer
- maternofetal autoimmunity
- developmental delay
- epilepsy
