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DC Field | Value | Language |
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dc.contributor.author | Olivera Ardid, Sara | - |
dc.contributor.author | Bello Gil, Daniel | - |
dc.contributor.author | Tuzikov, Alexander | - |
dc.contributor.author | Araujo, Ricardo N. | - |
dc.contributor.author | Ferrero Alves, Yara | - |
dc.contributor.author | García Figueroa, Blanca Esther | - |
dc.contributor.author | Labrador Horrillo, Moisés | - |
dc.contributor.author | García Pérez, Ana L. | - |
dc.contributor.author | Bovin, Nicolai | - |
dc.contributor.author | Mañez, Rafael | - |
dc.date.accessioned | 2022-05-13T08:47:07Z | - |
dc.date.available | 2022-05-13T08:47:07Z | - |
dc.date.issued | 2022-03-31 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | http://hdl.handle.net/2445/185585 | - |
dc.description.abstract | 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. | - |
dc.format.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.873019 | - |
dc.relation.ispartof | Frontiers in Immunology, 2022, vol. 13 | - |
dc.relation.uri | https://doi.org/10.3389/fimmu.2022.873019 | - |
dc.rights | cc by (c) Olivera Ardid, Saraet al, 2022 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Immunoteràpia | - |
dc.subject.classification | Al·lèrgia | - |
dc.subject.other | Immunotheraphy | - |
dc.subject.other | Allergy | - |
dc.title | Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2022-05-12T10:36:53Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 35432370 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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fimmu-13-873019.pdf | 4.38 MB | Adobe PDF | View/Open |
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