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...
| Autores: | , , , , , , , , , |
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| 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 |
| Sumario: | 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. |
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