{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:50:30Z","timestamp":1790952630981,"version":"4.1.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"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":"\n Background<\/jats:title>\n \n The IgG-degrading enzyme IdeS (imlifidase) is a cysteine protease produced by\n Streptococcus pyogenes<\/jats:italic>\n . It specifically hydrolyzes human IgG, cleaving the molecule to separate the F(ab\u2019)\n 2<\/jats:sub>\n fragment from the Fc region, thereby promoting IgG catabolism. The therapeutic form of IdeS (Idefirix\n \u00ae<\/jats:sup>\n ) is currently approved for use in patients undergoing kidney transplantation to eliminate donor-specific IgG, and in patients with Goodpasture syndrome to remove pathogenic anti-glomerular basement membrane antibodies. IgG antibodies directed against IdeS have been previously reported in both healthy individuals and kidney transplant recipients. However, the occurrence and potential clinical significance of anti-IdeS IgA antibodies and IdeS neutralizing antibodies have not been thoroughly investigated.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this study, we developed semi-quantitative enzyme-linked immunosorbent assays, synthesized a specific IdeS substrate, and validated a quantitative neutralization assay to detect and quantify anti-IdeS IgG, IgA, and IdeS neutralizing antibodies in healthy human plasma and serum samples.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n We demonstrate the presence of anti-IdeS IgG capable of neutralizing IdeS enzymatic activity in therapeutic preparations of pooled normal human IgG (IVIg). Anti-IdeS IgG and IgA antibodies were detected in the plasma and serum of over 85% of 136 healthy individuals. However, clinically significant levels of IdeS-neutralizing activity were found in only ~1% of the individuals tested. IdeS-neutralizing activity was mediated exclusively by IgG, not IgA, and did not systematically correlate with levels of anti-IdeS IgG.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Anti-IdeS IgG and IgA are highly prevalent in the normal population. This may relate to repeated infection by\n S. pyogenes<\/jats:italic>\n . However, we found a low prevalence of clinically relevant levels of IdeS neutralizing antibodies. These findings highlight the need for a prospective clinical trial to assess IdeS-binding and IdeS-neutralizing antibody levels in kidney transplant recipients. Our novel functional IdeS neutralization assay offers a predictive tool to guide personalized medicine and determine patient eligibility for IdeS-based desensitization protocols.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1728855","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:34:51Z","timestamp":1770615291000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel assays to assess the prevalence and neutralizing potential of anti-IdeS antibodies in healthy humans"],"prefix":"10.3389","volume":"17","author":[{"given":"Emna","family":"Hannachi","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre de Recherche des Cordeliers, Centre National de la Recherche Scientifique (CNRS), Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lia","family":"Trecco","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre de Recherche des Cordeliers, Centre National de la Recherche Scientifique (CNRS), Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Daventure","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre de Recherche des Cordeliers, Centre National de la Recherche Scientifique (CNRS), Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Delignat","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre de Recherche des Cordeliers, Centre National de la Recherche Scientifique (CNRS), Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre de Recherche des Cordeliers, Centre National de la Recherche Scientifique (CNRS), Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Lecerf","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre de Recherche des Cordeliers, Centre National de la Recherche Scientifique (CNRS), Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Thaunat","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Immunologie-infectiologie, Universit\u00e9 de Lyon, INSERM U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon","place":["Lyon, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan D.","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre de Recherche des Cordeliers, Centre National de la Recherche Scientifique (CNRS), Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Deligne","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre de Recherche des Cordeliers, 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