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Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in preclinical models.
Dejoux, Alice; Zhu, Qianqian; Ganneau, Christelle; Goff, Odile Richard-Le; Godon, Ophélie; Lemaitre, Julien; Relouzat, Francis; Huetz, François; Sokal, Aurélien; Vandenberghe, Alexis; Pecalvel, Cyprien; Hunault, Lise; Derenne, Thomas; Gillis, Caitlin M; Iannascoli, Bruno; Wang, Yidan; Rose, Thierry; Mertens, Christel; Nicaise-Roland, Pascale; England, Patrick; Mahévas, Matthieu; de Chaisemartin, Luc; Le Grand, Roger; Letscher, Hélène; Saul, Frederick; Pissis, Cédric; Haouz, Ahmed; Reber, Laurent L; Chappert, Pascal; Jönsson, Friederike; Ebo, Didier G; Millot, Gaël A; Bay, Sylvie; Chollet-Martin, Sylvie; Gouel-Chéron, Aurélie; Bruhns, Pierre.
Afiliación
  • Dejoux A; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • Zhu Q; Sorbonne Université, Collège Doctoral, 75005 Paris, France.
  • Ganneau C; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • Goff OR; Université Paris-Saclay, INSERM, Inflammation Microbiome Immunosurveillance, 91400 Orsay, France.
  • Godon O; Institut Pasteur, Université Paris Cité, CNRS UMR3523, Chimie des Biomolécules, 75015 Paris, France.
  • Lemaitre J; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • Relouzat F; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • Huetz F; Université Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases, 92260 Fontenay-aux-Roses and 94250 Le Kremlin-Bicêtre, France.
  • Sokal A; Université Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases, 92260 Fontenay-aux-Roses and 94250 Le Kremlin-Bicêtre, France.
  • Vandenberghe A; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • Pecalvel C; Institut Necker Enfants Malades, INSERM U1151/CNRS UMR 8253, Action thématique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, Université Paris Cité, Université Paris Est-Créteil, 94000 Créteil, France; INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale, Université
  • Hunault L; Service de Médecine interne, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris Cité, 92110 Clichy, France.
  • Derenne T; Institut Necker Enfants Malades, INSERM U1151/CNRS UMR 8253, Action thématique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, Université Paris Cité, Université Paris Est-Créteil, 94000 Créteil, France; INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale, Université
  • Gillis CM; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, University Toulouse III, 31000 Toulouse, France.
  • Iannascoli B; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • Wang Y; Sorbonne Université, Collège Doctoral, 75005 Paris, France.
  • Rose T; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • Mertens C; Sorbonne Université, Collège Doctoral, 75005 Paris, France.
  • Nicaise-Roland P; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • England P; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
  • Mahévas M; Institut Pasteur, Université Paris Cité, INSERM UMR1224, Biologie Cellulaire des Lymphocytes, Ligue Nationale Contre le Cancer, Équipe Labellisée Ligue 2018, 75015 Paris, France.
  • de Chaisemartin L; Faculty of Medicine and Health Science, Department of Immunology-Allergology-Rheumatology, Antwerp University Hospital and the Infla-Med Center of Excellence, University of Antwerp, Antwerp, Belgium; Department of Immunology and Allergology, AZ Jan Palfijn Ghent, 9000 Ghent, Belgium.
  • Le Grand R; Service d'immunologie Biologique, DMU BIOGEM, Hôpital Bichat, APHP, 75018, Paris, France.
  • Saul F; Institut Pasteur, Université Paris Cité, CNRS UMR3528, Molecular Biophysics Core Facility, 75015 Paris, France.
  • Pissis C; Institut Necker Enfants Malades, INSERM U1151/CNRS UMR 8253, Action thématique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, Université Paris Cité, Université Paris Est-Créteil, 94000 Créteil, France; INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale, Université
  • Haouz A; Université Paris-Saclay, INSERM, Inflammation Microbiome Immunosurveillance, 91400 Orsay, France.
  • Reber LL; Service d'immunologie Biologique, DMU BIOGEM, Hôpital Bichat, APHP, 75018, Paris, France.
  • Chappert P; Université Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases, 92260 Fontenay-aux-Roses and 94250 Le Kremlin-Bicêtre, France.
  • Jönsson F; Université Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases, 92260 Fontenay-aux-Roses and 94250 Le Kremlin-Bicêtre, France.
  • Ebo DG; Institut Pasteur, Université Paris Cité, CNRS UMR3528, Plate-forme Cristallographie-C2RT, 75015 Paris, France.
  • Millot GA; Institut Pasteur, Université Paris Cité, CNRS UMR3528, Plate-forme Cristallographie-C2RT, 75015 Paris, France.
  • Bay S; Institut Pasteur, Université Paris Cité, CNRS UMR3528, Plate-forme Cristallographie-C2RT, 75015 Paris, France.
  • Chollet-Martin S; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, University Toulouse III, 31000 Toulouse, France.
  • Gouel-Chéron A; Institut Necker Enfants Malades, INSERM U1151/CNRS UMR 8253, Action thématique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, Université Paris Cité, Université Paris Est-Créteil, 94000 Créteil, France; INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale, Université
  • Bruhns P; Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France.
Sci Transl Med ; 16(764): eado4463, 2024 Sep 11.
Article en En | MEDLINE | ID: mdl-39259810
ABSTRACT
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rocuronio / Anafilaxia Límite: Animals / Female / Humans / Male Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rocuronio / Anafilaxia Límite: Animals / Female / Humans / Male Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos