Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases

Anti-alpha Gal IgE antibodies mediate a spreading allergic condition known as alpha Gal-syndrome (AGS). People exposed to hard tick bites are sensitized to alpha Gal, producing elevated levels of anti-alpha Gal IgE, which are responsible for AGS. This work presents an immunotherapy based on polymeri...

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Autores: Olivera Ardid, Sara, Bello Gil, Daniel, Tuzikov, Alexander, Araujo, Ricardo N., Ferrero Alves, Yara, García Figueroa, Blanca Esther, Labrador Horrillo, Moisés, García Pérez, Ana L., Bovin, Nicolai, Mañez, Rafael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/185585
Acceso en línea:https://hdl.handle.net/2445/185585
Access Level:acceso abierto
Palabra clave:Immunoteràpia
Al·lèrgia
Immunotheraphy
Allergy
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spelling Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated DiseasesOlivera Ardid, SaraBello Gil, DanielTuzikov, AlexanderAraujo, Ricardo N.Ferrero Alves, YaraGarcía Figueroa, Blanca EstherLabrador Horrillo, MoisésGarcía Pérez, Ana L.Bovin, NicolaiMañez, RafaelImmunoteràpiaAl·lèrgiaImmunotheraphyAllergyAnti-alpha Gal IgE antibodies mediate a spreading allergic condition known as alpha Gal-syndrome (AGS). People exposed to hard tick bites are sensitized to alpha Gal, producing elevated levels of anti-alpha Gal IgE, which are responsible for AGS. This work presents an immunotherapy based on polymeric alpha Gal-glycoconjugates for potentially treating allergic disorders by selectively inhibiting anti-alpha Gal IgE antibodies. We synthesized a set of alpha Gal-glycoconjugates, based on poly-L-lysine of different degrees of polymerization (DP1000, DP600, and DP100), to specifically inhibit in vitro the anti-alpha Gal IgE antibodies in the serum of alpha Gal-sensitized patients (n=13). Moreover, an animal model for alpha Gal sensitization in GalT-KO mice was developed by intradermal administration of hard tick' salivary gland extract, mimicking the sensitization mechanism postulated in humans. The in vitro exposure to all polymeric glycoconjugates (5-10-20-50-100 mu g/mL) mainly inhibited anti-alpha Gal IgE and IgM isotypes, with a lower inhibition effect on the IgA and IgG, respectively. We demonstrated a differential anti-alpha Gal isotype inhibition as a function of the length of the poly-L-lysine and the number of alpha Gal residues exposed in the glycoconjugates. These results defined a minimum of 27 alpha Gal residues to inhibit most of the induced anti-alpha Gal IgE in vitro. Furthermore, the alpha Gal-glycoconjugate DP1000-RA0118 (10 mg/kg sc.) showed a high capacity to remove the anti-alpha Gal IgE antibodies (>= 75% on average) induced in GalT-KO mice, together with similar inhibition for circulating anti-alpha Gal IgG and IgM. Our study suggests the potential clinical use of poly-L-lysine-based alpha Gal-glycoconjugates for treating allergic disorders mediated by anti-alpha Gal IgE antibodies.Frontiers Media2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/185585Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.873019Frontiers in Immunology, 2022, vol. 13https://doi.org/10.3389/fimmu.2022.873019cc by (c) Olivera Ardid, Saraet al, 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1855852026-05-27T06:46:51Z
dc.title.none.fl_str_mv Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases
title Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases
spellingShingle Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases
Olivera Ardid, Sara
Immunoteràpia
Al·lèrgia
Immunotheraphy
Allergy
title_short Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases
title_full Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases
title_fullStr Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases
title_full_unstemmed Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases
title_sort Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases
dc.creator.none.fl_str_mv Olivera Ardid, Sara
Bello Gil, Daniel
Tuzikov, Alexander
Araujo, Ricardo N.
Ferrero Alves, Yara
García Figueroa, Blanca Esther
Labrador Horrillo, Moisés
García Pérez, Ana L.
Bovin, Nicolai
Mañez, Rafael
author Olivera Ardid, Sara
author_facet Olivera Ardid, Sara
Bello Gil, Daniel
Tuzikov, Alexander
Araujo, Ricardo N.
Ferrero Alves, Yara
García Figueroa, Blanca Esther
Labrador Horrillo, Moisés
García Pérez, Ana L.
Bovin, Nicolai
Mañez, Rafael
author_role author
author2 Bello Gil, Daniel
Tuzikov, Alexander
Araujo, Ricardo N.
Ferrero Alves, Yara
García Figueroa, Blanca Esther
Labrador Horrillo, Moisés
García Pérez, Ana L.
Bovin, Nicolai
Mañez, Rafael
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Immunoteràpia
Al·lèrgia
Immunotheraphy
Allergy
topic Immunoteràpia
Al·lèrgia
Immunotheraphy
Allergy
description Anti-alpha Gal IgE antibodies mediate a spreading allergic condition known as alpha Gal-syndrome (AGS). People exposed to hard tick bites are sensitized to alpha Gal, producing elevated levels of anti-alpha Gal IgE, which are responsible for AGS. This work presents an immunotherapy based on polymeric alpha Gal-glycoconjugates for potentially treating allergic disorders by selectively inhibiting anti-alpha Gal IgE antibodies. We synthesized a set of alpha Gal-glycoconjugates, based on poly-L-lysine of different degrees of polymerization (DP1000, DP600, and DP100), to specifically inhibit in vitro the anti-alpha Gal IgE antibodies in the serum of alpha Gal-sensitized patients (n=13). Moreover, an animal model for alpha Gal sensitization in GalT-KO mice was developed by intradermal administration of hard tick' salivary gland extract, mimicking the sensitization mechanism postulated in humans. The in vitro exposure to all polymeric glycoconjugates (5-10-20-50-100 mu g/mL) mainly inhibited anti-alpha Gal IgE and IgM isotypes, with a lower inhibition effect on the IgA and IgG, respectively. We demonstrated a differential anti-alpha Gal isotype inhibition as a function of the length of the poly-L-lysine and the number of alpha Gal residues exposed in the glycoconjugates. These results defined a minimum of 27 alpha Gal residues to inhibit most of the induced anti-alpha Gal IgE in vitro. Furthermore, the alpha Gal-glycoconjugate DP1000-RA0118 (10 mg/kg sc.) showed a high capacity to remove the anti-alpha Gal IgE antibodies (>= 75% on average) induced in GalT-KO mice, together with similar inhibition for circulating anti-alpha Gal IgG and IgM. Our study suggests the potential clinical use of poly-L-lysine-based alpha Gal-glycoconjugates for treating allergic disorders mediated by anti-alpha Gal IgE antibodies.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/185585
url https://hdl.handle.net/2445/185585
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.873019
Frontiers in Immunology, 2022, vol. 13
https://doi.org/10.3389/fimmu.2022.873019
dc.rights.none.fl_str_mv cc by (c) Olivera Ardid, Saraet al, 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Olivera Ardid, Saraet al, 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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