Brain, Behavior, & Immunity - Health (Nov 2023)
Synapsin autoantibodies during pregnancy are associated with fetal abnormalities
- Isabel Bünger,
- Ivan Talucci,
- Jakob Kreye,
- Markus Höltje,
- Konstantin L. Makridis,
- Helle Foverskov Rasmussen,
- Scott van Hoof,
- César Cordero-Gomez,
- Tim Ullrich,
- Eva Sedlin,
- Kai Oliver Kreissner,
- Christian Hoffmann,
- Dragomir Milovanovic,
- Paul Turko,
- Friedemann Paul,
- Jessica Meckies,
- Stefan Verlohren,
- Wolfgang Henrich,
- Rabih Chaoui,
- Hans Michael Maric,
- Angela M. Kaindl,
- Harald Prüss
Affiliations
- Isabel Bünger
- German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Ivan Talucci
- Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, University of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany
- Jakob Kreye
- German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Berlin Institute of Health (BIH), 10178, Berlin, Germany; Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Center for Chronically Sick Children, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Markus Höltje
- Institute of Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Konstantin L. Makridis
- Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Center for Chronically Sick Children, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Institute of Cell Biology and Neurobiology, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Helle Foverskov Rasmussen
- German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Scott van Hoof
- German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- César Cordero-Gomez
- German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Tim Ullrich
- Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Center for Chronically Sick Children, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Eva Sedlin
- Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Center for Chronically Sick Children, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Department of Neonatology, Helios Klinikum, Berlin-Buch, Germany
- Kai Oliver Kreissner
- Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, University of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany
- Christian Hoffmann
- German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany
- Dragomir Milovanovic
- German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany
- Paul Turko
- Institute of Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Friedemann Paul
- NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany
- Jessica Meckies
- Gynecology Practice Frauenärztinnen am Schloß, 12163, Berlin, Germany
- Stefan Verlohren
- Department of Obstetrics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Wolfgang Henrich
- Department of Obstetrics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Rabih Chaoui
- Center for Prenatal Diagnosis and Human Genetics, 10719, Berlin, Germany
- Hans Michael Maric
- Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, University of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany
- Angela M. Kaindl
- Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Center for Chronically Sick Children, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Institute of Cell Biology and Neurobiology, Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
- Harald Prüss
- German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117, Berlin, Germany; Corresponding author. German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117, Berlin, Germany.
- Journal volume & issue
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Vol. 33
p. 100678
Abstract
Anti-neuronal autoantibodies can be transplacentally transferred during pregnancy and may cause detrimental effects on fetal development. It is unclear whether autoantibodies against synapsin-I, one of the most abundant synaptic proteins, are associated with developmental abnormalities in humans. We recruited a cohort of 263 pregnant women and detected serum synapsin-I IgG autoantibodies in 13.3% using cell-based assays. Seropositivity was strongly associated with abnormalities of fetal development including structural defects, intrauterine growth retardation, amniotic fluid disorders and neuropsychiatric developmental diseases in previous children (odds ratios of 3–6.5). Autoantibodies reached the fetal circulation and were mainly of IgG1/IgG3 subclasses. They bound to conformational and linear synapsin-I epitopes, five distinct epitopes were identified using peptide microarrays. The findings indicate that synapsin-I autoantibodies may be clinically useful biomarkers or even directly participate in the disease process of neurodevelopmental disorders, thus being potentially amenable to antibody-targeting interventional strategies in the future.
