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fimmu-13-873019.pdf (4.27 MB)

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Data de publicació

2022-03-31

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cc by (c) Olivera Ardid, Saraet al, 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/185585

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

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Recurs relacionat

https://doi.org/10.3389/fimmu.2022.873019

Resum

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.

Matèries

Immunoteràpia, Al·lèrgia

Matèries (anglès)

Immunotheraphy, Allergy

Citació

Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

OLIVERA ARDID, Sara, et al. Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases. Frontiers in Immunology. 2022. Vol. 13. ISSN 1664-3224. [consulted: 3 of August of 2026]. Available at: https://hdl.handle.net/2445/185585

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