{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:21:23Z","timestamp":1779294083264,"version":"3.51.4"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Anti-\u03b1Gal IgE antibodies mediate a spreading allergic condition known as \u03b1Gal-syndrome (AGS). People exposed to hard tick bites are sensitized to \u03b1Gal, producing elevated levels of anti-\u03b1Gal IgE, which are responsible for AGS. This work presents an immunotherapy based on polymeric \u03b1Gal-glycoconjugates for potentially treating allergic disorders by selectively inhibiting anti-\u03b1Gal IgE antibodies. We synthesized a set of \u03b1Gal-glycoconjugates, based on poly-L-lysine of different degrees of polymerization (DP1000, DP600, and DP100), to specifically inhibit <jats:italic>in vitro<\/jats:italic> the anti-\u03b1Gal IgE antibodies in the serum of \u03b1Gal-sensitized patients (n=13). Moreover, an animal model for \u03b1Gal sensitization in GalT-KO mice was developed by intradermal administration of hard tick\u2019 salivary gland extract, mimicking the sensitization mechanism postulated in humans. The <jats:italic>in vitro<\/jats:italic> exposure to all polymeric glycoconjugates (5-10-20-50-100 \u00b5g\/mL) mainly inhibited anti-\u03b1Gal IgE and IgM isotypes, with a lower inhibition effect on the IgA and IgG, respectively. We demonstrated a differential anti-\u03b1Gal isotype inhibition as a function of the length of the poly-L-lysine and the number of \u03b1Gal residues exposed in the glycoconjugates. These results defined a minimum of 27 \u03b1Gal residues to inhibit most of the induced anti-\u03b1Gal IgE <jats:italic>in vitro<\/jats:italic>. Furthermore, the \u03b1Gal-glycoconjugate DP1000-RA0118 (10 mg\/kg sc.) showed a high capacity to remove the anti-\u03b1Gal IgE antibodies (\u226575% on average) induced in GalT-KO mice, together with similar inhibition for circulating anti-\u03b1Gal IgG and IgM. Our study suggests the potential clinical use of poly-L-lysine-based \u03b1Gal-glycoconjugates for treating allergic disorders mediated by anti-\u03b1Gal IgE antibodies.<\/jats:p>","DOI":"10.3389\/fimmu.2022.873019","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T15:27:07Z","timestamp":1648740427000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Poly-L-Lysine-Based \u03b1Gal-Glycoconjugates for Treating Anti-\u03b1Gal IgE-Mediated Diseases"],"prefix":"10.3389","volume":"13","author":[{"given":"Sara","family":"Olivera-Ardid","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Bello-Gil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Tuzikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo N.","family":"Araujo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yara","family":"Ferrero-Alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanca Esther","family":"Garc\u00eda Figueroa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mois\u00e9s","family":"Labrador-Horrillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana L.","family":"Garc\u00eda-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolai","family":"Bovin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Ma\u00f1ez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13601-018-0213-z","article-title":"Anti-IgE Therapy for IgE-Mediated Allergic Diseases: From Neutralizing IgE Antibodies to Eliminating IgE+B Cells","volume":"8","author":"Hu","year":"2018","journal-title":"Clin Transl Allergy"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/all.14476","article-title":"The Effects of Climate Change on Respiratory Allergy and Asthma Induced by Pollen and Mold Allergens","volume":"75","author":"D\u2019Amato","year":"2020","journal-title":"Allergy Eur J Allergy Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jaci.2017.11.003","article-title":"Food Allergy: A Review and Update on Epidemiology, Pathogenesis, Diagnosis, Prevention, and Management","volume":"141","author":"Sicherer","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/all.12406","article-title":"Global Allergy Forum and Second Davos Declaration 2013 Allergy: Barriers to Cure - 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