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Protective anti‐prion antibodies in human immunoglobulin repertoires
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506995/ https://www.ncbi.nlm.nih.gov/pubmed/32776637 http://dx.doi.org/10.15252/emmm.202012739 |
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author | Senatore, Assunta Frontzek, Karl Emmenegger, Marc Chincisan, Andra Losa, Marco Reimann, Regina Horny, Geraldine Guo, Jingjing Fels, Sylvie Sorce, Silvia Zhu, Caihong George, Nathalie Ewert, Stefan Pietzonka, Thomas Hornemann, Simone Aguzzi, Adriano |
author_facet | Senatore, Assunta Frontzek, Karl Emmenegger, Marc Chincisan, Andra Losa, Marco Reimann, Regina Horny, Geraldine Guo, Jingjing Fels, Sylvie Sorce, Silvia Zhu, Caihong George, Nathalie Ewert, Stefan Pietzonka, Thomas Hornemann, Simone Aguzzi, Adriano |
author_sort | Senatore, Assunta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7506995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75069952020-09-28 Protective anti‐prion antibodies in human immunoglobulin repertoires Senatore, Assunta Frontzek, Karl Emmenegger, Marc Chincisan, Andra Losa, Marco Reimann, Regina Horny, Geraldine Guo, Jingjing Fels, Sylvie Sorce, Silvia Zhu, Caihong George, Nathalie Ewert, Stefan Pietzonka, Thomas Hornemann, Simone Aguzzi, Adriano EMBO Mol Med Articles 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. John Wiley and Sons Inc. 2020-08-10 2020-09-07 /pmc/articles/PMC7506995/ /pubmed/32776637 http://dx.doi.org/10.15252/emmm.202012739 Text en © 2020 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Senatore, Assunta Frontzek, Karl Emmenegger, Marc Chincisan, Andra Losa, Marco Reimann, Regina Horny, Geraldine Guo, Jingjing Fels, Sylvie Sorce, Silvia Zhu, Caihong George, Nathalie Ewert, Stefan Pietzonka, Thomas Hornemann, Simone Aguzzi, Adriano Protective anti‐prion antibodies in human immunoglobulin repertoires |
title | Protective anti‐prion antibodies in human immunoglobulin repertoires |
title_full | Protective anti‐prion antibodies in human immunoglobulin repertoires |
title_fullStr | Protective anti‐prion antibodies in human immunoglobulin repertoires |
title_full_unstemmed | Protective anti‐prion antibodies in human immunoglobulin repertoires |
title_short | Protective anti‐prion antibodies in human immunoglobulin repertoires |
title_sort | protective anti‐prion antibodies in human immunoglobulin repertoires |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506995/ https://www.ncbi.nlm.nih.gov/pubmed/32776637 http://dx.doi.org/10.15252/emmm.202012739 |
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