Novel assays to assess the prevalence and neutralizing potential of anti-IdeS antibodies in healthy humans.

Authors

Emna Hannachi, Amélia Trecco, Victoria Daventure, Sandrine Delignat, Perrine Bonilla, Maxime Lecerf, Olivier Thaunat, Jordan D Dimitrov, Claire Deligne, Sébastien Lacroix-Desmazes

Published in

Frontiers in immunology. Volume 17. Pages 1728855. Epub Feb 09, 2026.

Abstract

The IgG-degrading enzyme IdeS (imlifidase) is a cysteine protease produced by Streptococcus pyogenes. It specifically hydrolyzes human IgG, cleaving the molecule to separate the F(ab')₂ fragment from the Fc region, thereby promoting IgG catabolism. The therapeutic form of IdeS (Idefirix^®) 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.
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.
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.
Anti-IdeS IgG and IgA are highly prevalent in the normal population. This may relate to repeated infection by S. pyogenes. 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.

PMID:
41737221
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

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