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

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

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Authors: Olivera-Ardid, Sara|||0000-0002-6185-5331, Bello-Gil, Daniel, Tuzikov, Alexander, Araujo, Ricardo N., Ferrero-Alves, Yara, García Figueroa, Blanca Esther, Labrador Horrillo, Moises|||0000-0003-3222-2380, García-Pérez, Ana L., Bovin, Nicolai, Mañez, Rafael
Format: article
Publication Date:2022
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:258081
Online Access:https://ddd.uab.cat/record/258081
https://dx.doi.org/urn:doi:10.3389/fimmu.2022.873019
Access Level:Open access
Keyword:αGal-syndrome
Poly-l-lysine-based αGal-glycoconjugates
Anti-αgal IgE inhibition
GalT-KO mice
Immunotherapy
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spelling Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated DiseasesOlivera-Ardid, Sara|||0000-0002-6185-5331Bello-Gil, DanielTuzikov, AlexanderAraujo, Ricardo N.Ferrero-Alves, YaraGarcía Figueroa, Blanca EstherLabrador Horrillo, Moises|||0000-0003-3222-2380García-Pérez, Ana L.Bovin, NicolaiMañez, RafaelαGal-syndromePoly-l-lysine-based αGal-glycoconjugatesAnti-αgal IgE inhibitionGalT-KO miceImmunotherapyAnti-αGal IgE antibodies mediate a spreading allergic condition known as αGal-syndrome (AGS). People exposed to hard tick bites are sensitized to αGal, producing elevated levels of anti-αGal IgE, which are responsible for AGS. This work presents an immunotherapy based on polymeric αGal-glycoconjugates for potentially treating allergic disorders by selectively inhibiting anti-αGal IgE antibodies. We synthesized a set of αGal-glycoconjugates, based on poly-L-lysine of different degrees of polymerization (DP1000, DP600, and DP100), to specifically inhibit in vitro the anti-αGal IgE antibodies in the serum of αGal-sensitized patients (n=13). Moreover, an animal model for αGal 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 µg/mL) mainly inhibited anti-αGal IgE and IgM isotypes, with a lower inhibition effect on the IgA and IgG, respectively. We demonstrated a differential anti-αGal isotype inhibition as a function of the length of the poly-L-lysine and the number of αGal residues exposed in the glycoconjugates. These results defined a minimum of 27 αGal residues to inhibit most of the induced anti-αGal IgE in vitro. Furthermore, the αGal-glycoconjugate DP1000-RA0118 (10 mg/kg sc.) showed a high capacity to remove the anti-αGal IgE antibodies (≥75% on average) induced in GalT-KO mice, together with similar inhibition for circulating anti-αGal IgG and IgM. Our study suggests the potential clinical use of poly-L-lysine-based αGal-glycoconjugates for treating allergic disorders mediated by anti-αGal IgE antibodies.Universitat Autònoma de Barcelona. Departament de Medicina 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/258081https://dx.doi.org/urn:doi:10.3389/fimmu.2022.873019reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2580812026-06-06T12:50:31Z
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|||0000-0002-6185-5331
αGal-syndrome
Poly-l-lysine-based αGal-glycoconjugates
Anti-αgal IgE inhibition
GalT-KO mice
Immunotherapy
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|||0000-0002-6185-5331
Bello-Gil, Daniel
Tuzikov, Alexander
Araujo, Ricardo N.
Ferrero-Alves, Yara
García Figueroa, Blanca Esther
Labrador Horrillo, Moises|||0000-0003-3222-2380
García-Pérez, Ana L.
Bovin, Nicolai
Mañez, Rafael
author Olivera-Ardid, Sara|||0000-0002-6185-5331
author_facet Olivera-Ardid, Sara|||0000-0002-6185-5331
Bello-Gil, Daniel
Tuzikov, Alexander
Araujo, Ricardo N.
Ferrero-Alves, Yara
García Figueroa, Blanca Esther
Labrador Horrillo, Moises|||0000-0003-3222-2380
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, Moises|||0000-0003-3222-2380
García-Pérez, Ana L.
Bovin, Nicolai
Mañez, Rafael
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Medicina
dc.subject.none.fl_str_mv αGal-syndrome
Poly-l-lysine-based αGal-glycoconjugates
Anti-αgal IgE inhibition
GalT-KO mice
Immunotherapy
topic αGal-syndrome
Poly-l-lysine-based αGal-glycoconjugates
Anti-αgal IgE inhibition
GalT-KO mice
Immunotherapy
description Anti-αGal IgE antibodies mediate a spreading allergic condition known as αGal-syndrome (AGS). People exposed to hard tick bites are sensitized to αGal, producing elevated levels of anti-αGal IgE, which are responsible for AGS. This work presents an immunotherapy based on polymeric αGal-glycoconjugates for potentially treating allergic disorders by selectively inhibiting anti-αGal IgE antibodies. We synthesized a set of αGal-glycoconjugates, based on poly-L-lysine of different degrees of polymerization (DP1000, DP600, and DP100), to specifically inhibit in vitro the anti-αGal IgE antibodies in the serum of αGal-sensitized patients (n=13). Moreover, an animal model for αGal 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 µg/mL) mainly inhibited anti-αGal IgE and IgM isotypes, with a lower inhibition effect on the IgA and IgG, respectively. We demonstrated a differential anti-αGal isotype inhibition as a function of the length of the poly-L-lysine and the number of αGal residues exposed in the glycoconjugates. These results defined a minimum of 27 αGal residues to inhibit most of the induced anti-αGal IgE in vitro. Furthermore, the αGal-glycoconjugate DP1000-RA0118 (10 mg/kg sc.) showed a high capacity to remove the anti-αGal IgE antibodies (≥75% on average) induced in GalT-KO mice, together with similar inhibition for circulating anti-αGal IgG and IgM. Our study suggests the potential clinical use of poly-L-lysine-based αGal-glycoconjugates for treating allergic disorders mediated by anti-αGal IgE antibodies.
publishDate 2022
dc.date.none.fl_str_mv 2
2022-01-01
2022
2022-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/258081
https://dx.doi.org/urn:doi:10.3389/fimmu.2022.873019
url https://ddd.uab.cat/record/258081
https://dx.doi.org/urn:doi:10.3389/fimmu.2022.873019
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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