Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in preclinical models - Institut Pasteur
Article Dans Une Revue Science Translational Medicine Année : 2024

Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in preclinical models

David Mancardi
  • Fonction : Collaborateur
Vanessa Granger
  • Fonction : Collaborateur
Dan Longrois
  • Fonction : Collaborateur
Philippe Montravers
  • Fonction : Collaborateur
Caroline Sauvan
  • Fonction : Collaborateur
Michel Aubier
  • Fonction : Collaborateur
Catherine Neukirch
  • Fonction : Collaborateur
Fadia Dib
  • Fonction : Collaborateur
Catherine Paugam-Burtz
  • Fonction : Collaborateur
Skander Necib
  • Fonction : Collaborateur
Hawa Keita-Meyer
  • Fonction : Collaborateur
Valentina Faitot
  • Fonction : Collaborateur
Alexandre Mebazaa
  • Fonction : Collaborateur
Matthieu Le Dorze
  • Fonction : Collaborateur
Bernard Cholley
  • Fonction : Collaborateur
Jean Mantz
  • Fonction : Collaborateur
Olivier Langeron
  • Fonction : Collaborateur
Sabrine Roche
  • Fonction : Collaborateur
Laurent Jacob
  • Fonction : Collaborateur
Benoit Plaud
  • Fonction : Collaborateur
Julie Bresson
  • Fonction : Collaborateur
Carole Chahine
  • Fonction : Collaborateur
Marc Fischler
  • Fonction : Collaborateur
Marie-Thérèse Guinnepain
  • Fonction : Collaborateur
Florence Tubach
  • Fonction : Collaborateur
Antoine Mignon
  • Fonction : Collaborateur

Résumé

Neuromuscular blocking agents (NMBAs) relax skeletal muscles to facilitate surgeries and ease intubation but can lead to adverse reactions, including complications because of postoperative residual neuromuscular blockade (rNMB) and, in rare cases, anaphylaxis. Both adverse reactions vary between types of NMBAs, with rocuronium, a widely used nondepolarizing NMBA, inducing one of the longest rNMB durations and highest anaphylaxis incidences. rNMB induced by rocuronium can be reversed by the synthetic γ-cyclodextrin sugammadex. However, in rare cases, sugammadex can provoke anaphylaxis. Thus, additional therapeutic options are needed. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies. To understand the pathogenesis of rocuronium-induced anaphylaxis and to identify potential therapeutics, we investigated the memory B cell antibody repertoire of patients with suspected hypersensitivity to rocuronium. We identified polyclonal antibody repertoires with a high diversity among V(D)J genes without evidence of clonal groups. When recombinantly expressed, these antibodies demonstrated specificity and low affinity for rocuronium without cross-reactivity for other NMBAs. Moreover, when these antibodies were expressed as human immunoglobulin E (IgE), they triggered human mast cell activation and passive systemic anaphylaxis in transgenic mice, although their affinities were insufficient to serve as reversal agents. Rocuronium-specific, high-affinity antibodies were thus isolated from rocuronium-immunized mice. The highest-affinity antibody was able to reverse rocuronium-induced neuromuscular blockade in nonhuman primates with kinetics comparable to that of sugammadex. Together, these data support the hypothesis that antibodies cause anaphylactic reactions to rocuronium and pave the way for improved diagnostics and neuromuscular blockade reversal agents.
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pasteur-04706288 , version 1 (23-09-2024)

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Alice Dejoux, Qianqian Zhu, Christelle Ganneau, Odile Richard-Le Goff, Ophélie Godon, et al.. Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in preclinical models. Science Translational Medicine, 2024, 16 (764), pp.eado4463. ⟨10.1126/scitranslmed.ado4463⟩. ⟨pasteur-04706288⟩
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