Protective anti‐prion antibodies in human immunoglobulin repertoires
| Autor: | Simone Hornemann, Silvia Sorce, Caihong Zhu, Assunta Senatore, Karl Frontzek, Adriano Aguzzi, Marc Emmenegger, Sylvie Fels, Stefan Ewert, Marco Losa, Jingjing Guo, Geraldine Horny, Andra Chincisan, Nathalie George, Regina Reimann, Thomas Pietzonka |
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| Přispěvatelé: | University of Zurich, Hornemann, Simone, Aguzzi, Adriano |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Medicine (General) Phage display Prions medicine.medical_treatment animal diseases Immunology prion disease 10208 Institute of Neuropathology next‐generation sequencing 610 Medicine & health Biology QH426-470 medicine.disease_cause Neuroprotection Epitope Article Antibodies Autoimmunity PRNP Prion Diseases 03 medical and health sciences 0302 clinical medicine R5-920 medicine Genetics Humans B-Lymphocytes Immunotherapy Articles Molecular medicine 3. Good health nervous system diseases human immunological repertoires 030104 developmental biology 1313 Molecular Medicine biology.protein 570 Life sciences biology Molecular Medicine anti‐PrP antibodies Antibody phage display 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | EMBO Molecular Medicine, Vol 12, Iss 9, Pp n/a-n/a (2020) EMBO Molecular Medicine |
| ISSN: | 1757-4676 1757-4684 |
| Popis: | Prion immunotherapy may hold great potential, but antibodies against certain PrP epitopes can be neurotoxic. Here, we identified > 6,000 PrP‐binding antibodies in a synthetic human Fab phage display library, 49 of which we characterized in detail. Antibodies directed against the flexible tail of PrP conferred neuroprotection against infectious prions. We then mined published repertoires of circulating B cells from healthy humans and found antibodies similar to the protective phage‐derived antibodies. When expressed recombinantly, these antibodies exhibited anti‐PrP reactivity. Furthermore, we surveyed 48,718 samples from 37,894 hospital patients for the presence of anti‐PrP IgGs and found 21 high‐titer individuals. The clinical files of these individuals did not reveal any enrichment of specific pathologies, suggesting that anti‐PrP autoimmunity is innocuous. The existence of anti‐prion antibodies in unbiased human immunological repertoires suggests that they might clear nascent prions early in life. Combined with the reported lack of such antibodies in carriers of disease‐associated PRNP mutations, this suggests a link to the low incidence of spontaneous prion diseases in human populations. This study assessed the anti‐prion protein (PrP) immunoreactivity in human immunoglobulin repertoires and patient samples. Anti‐PrP autoimmunity can exist in human communities, appears to be innocuous, and may protect against prion infections. |
| Databáze: | OpenAIRE |
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