Synapsin autoantibodies during pregnancy are associated with fetal abnormalities
Year: 2023
Type: article
Study design: Observational Study
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.
Authors: 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
Institutions: German Center for Neurodegenerative Diseases, Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité – Universitätsmedizin Berlin, University of Würzburg, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Helios Hospital Berlin-Buch, Max Delbrück Center, Zentrum für Pränataldiagnostik
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutsches Zentrum für Neurodegenerative Erkrankungen, Einstein Stiftung Berlin, Julius-Maximilians-Universität Würzburg, Helmholtz Association, Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg, Istituto Italiano di Tecnologia, Berlin Institute of Health, Graduate School of Life Sciences, Julius-Maximilians-Universität Würzburg
Awards: G1380736555, G1967006974, G2504082584, G2735672739, G2815284267, G31261541, G3232879379, G4432942619, G4439705501, G6102503512, G664677429, G7027221778, CONNECT-GENERATE - Deutsches Netzwerk zur Erforschung autoimmuner Enzephalitiden - Teilprojekt 4 Autoantikörper, Teilprojekt 6 MRT-Bildgebung
OpenAlex ID: W4386248123