{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:39:30Z","timestamp":1791362370124,"version":"4.3.1"},"reference-count":94,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"764","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,9,11]]},"abstract":"<jats:p>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 \u03b3-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.<\/jats:p>","DOI":"10.1126\/scitranslmed.ado4463","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T17:59:08Z","timestamp":1726077548000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in preclinical models"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6715-633X","authenticated-orcid":true,"given":"Alice","family":"Dejoux","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France."},{"name":"Sorbonne Universit\u00e9, Coll\u00e8ge Doctoral, 75005 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-4954","authenticated-orcid":true,"given":"Qianqian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France."},{"name":"Universit\u00e9 Paris-Saclay, INSERM, Inflammation Microbiome Immunosurveillance, 91400 Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Ganneau","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3523, Chimie des Biomol\u00e9cules, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-2375","authenticated-orcid":true,"given":"Odile Richard-Le","family":"Goff","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1511-3764","authenticated-orcid":true,"given":"Oph\u00e9lie","family":"Godon","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6239-0110","authenticated-orcid":true,"given":"Julien","family":"Lemaitre","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases, 92260 Fontenay-aux-Roses and 94250 Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6387-8481","authenticated-orcid":true,"given":"Francis","family":"Relouzat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases, 92260 Fontenay-aux-Roses and 94250 Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8704-1881","authenticated-orcid":true,"given":"Fran\u00e7ois","family":"Huetz","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-8689","authenticated-orcid":true,"given":"Aur\u00e9lien","family":"Sokal","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151\/CNRS UMR 8253, Action th\u00e9matique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, Universit\u00e9 Paris Cit\u00e9, Universit\u00e9 Paris Est-Cr\u00e9teil, 94000 Cr\u00e9teil, France; INSERM U955, \u00e9quipe 2. 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