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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.
Afiliación
  • Senatore A; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Frontzek K; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Emmenegger M; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Chincisan A; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Losa M; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Reimann R; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Horny G; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Guo J; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Fels S; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Sorce S; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Zhu C; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • George N; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Ewert S; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Pietzonka T; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • Hornemann S; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Aguzzi A; Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
EMBO Mol Med ; 12(9): e12739, 2020 09 07.
Article en En | MEDLINE | ID: mdl-32776637
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Priones / Enfermedades por Prión Límite: Humans Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Priones / Enfermedades por Prión Límite: Humans Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido