Synapsin autoantibodies during pregnancy are associated with fetal abnormalities
Open accessPublished version of a preprint
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.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy
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- Authors
- Bünger, I., Talucci, I., Kreye, J., Höltje, M., Makridis, K. L., Foverskov Rasmussen, H., van Hoof, S., Cordero-Gomez, C., Ullrich, T., Sedlin, E., Kreissner, K. O., Hoffmann, C., Milovanovic, D., Turko, P., Paul, F., Meckies, J., Verlohren, S., Henrich, W., Chaoui, R., Maric, H. M., Kaindl, A. M., & Prüss, H.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- University of Würzburg (DE)
- Humboldt-Universität zu Berlin (DE)
- Max Delbrück Center (DE)
- Zentrum für Pränataldiagnostik (DE)
- Corresponding author
- Prüss, Harald
- ORCID
- Venue
- Brain, Behavior, & Immunity - Health
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 33
- Pages
- 100678
- ISSN
- 2666-3546 (ISSN-L)
- PMC
- PMC10483408
- OpenAlex
- W4386248123
- Cited by
- 5
- References
- 2
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain Behavior & Immunity - Health (publishedVersion, cc-by-nc-nd)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- DZNE Pub (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Einstein Foundation Berlin
- Bundesministerium für Bildung und Forschung (01GM1908D)
- Deutsche Forschungsgemeinschaft (MA6957/1-1, FOR 3004, PR1274/4-1, PR1274/9-1, PR1274/5-1)
- Berlin Institute of Health
- University of Würzburg Graduate School of Life Sciences
- Helmholtz Association of German Research Centres (HIL-A03)
- Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg (A-F-N-419)
- Deutsches Zentrum für Neurodegenerative Erkrankungen (1286/B10, SFB MI 2104)
- Topics
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- synapsin I, autoantibodies, pregnancy, transplacental transfer, fetal development, fetal growth restriction, amniotic fluid disorders, IgG subclasses, antigenic determinants, biomarkers, neurodevelopmental disorders, synaptic proteins
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