Frontiers in Immunology (Jul 2021)
Novel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones
- Jessy Elst,
- Jessy Elst,
- Marcus Maurer,
- Vito Sabato,
- Vito Sabato,
- Vito Sabato,
- Margaretha A. Faber,
- Margaretha A. Faber,
- Chris H. Bridts,
- Chris H. Bridts,
- Christel Mertens,
- Christel Mertens,
- Michel Van Houdt,
- Michel Van Houdt,
- Athina L. Van Gasse,
- Athina L. Van Gasse,
- Athina L. Van Gasse,
- Marie-Line M. van der Poorten,
- Marie-Line M. van der Poorten,
- Marie-Line M. van der Poorten,
- Leander P. De Puysseleyr,
- Leander P. De Puysseleyr,
- Margo M. Hagendorens,
- Margo M. Hagendorens,
- Margo M. Hagendorens,
- Viggo F. Van Tendeloo,
- Eva Lion,
- Diana Campillo-Davo,
- Didier G. Ebo,
- Didier G. Ebo,
- Didier G. Ebo
Affiliations
- Jessy Elst
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Jessy Elst
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Marcus Maurer
- Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin, Berlin, Germany
- Vito Sabato
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Vito Sabato
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Vito Sabato
- Department of Immunology, AZ Jan Palfijn Hospital Gent, Ghent, Belgium
- Margaretha A. Faber
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Margaretha A. Faber
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Chris H. Bridts
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Chris H. Bridts
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Christel Mertens
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Christel Mertens
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Michel Van Houdt
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Michel Van Houdt
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Athina L. Van Gasse
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Athina L. Van Gasse
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Athina L. Van Gasse
- Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
- Marie-Line M. van der Poorten
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Marie-Line M. van der Poorten
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Marie-Line M. van der Poorten
- Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
- Leander P. De Puysseleyr
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Leander P. De Puysseleyr
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Margo M. Hagendorens
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Margo M. Hagendorens
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Margo M. Hagendorens
- Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
- Viggo F. Van Tendeloo
- Laboratory of Experimental Hematology, Vaccine & Infectious Disease institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Eva Lion
- Laboratory of Experimental Hematology, Vaccine & Infectious Disease institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Diana Campillo-Davo
- Laboratory of Experimental Hematology, Vaccine & Infectious Disease institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Didier G. Ebo
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Didier G. Ebo
- Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
- Didier G. Ebo
- Department of Immunology, AZ Jan Palfijn Hospital Gent, Ghent, Belgium
- DOI
- https://doi.org/10.3389/fimmu.2021.668962
- Journal volume & issue
-
Vol. 12
Abstract
Neuromuscular blocking agents (NMBAs) like atracurium and rocuronium as well as fluoroquinolones (FQs) cause mast cell-mediated anaphylaxis by activating Mas-related G protein-coupled receptor X2 (MRGPRX2), but many questions remain unanswered. Here, we address three of them, namely whether primary human mast cells show similar activation by these drugs as murine mast cells and mast cell lines, how sugammadex protects from atracurium-induced MRGPRX2-mediated mast cell activation, and why some but not all patients treated with rocuronium develop anaphylaxis. We used peripheral blood-derived cultured mast cells from healthy donors and patients, assessed mast cell activation and degranulation by quantifying intracellular calcium and CD63 expression, respectively, and made use of MRGPRX2-silencing, via electroporation with Dicer-substrate small interfering RNAs, and single cell flow cytometric analyses. Atracurium, ciprofloxacin, and levofloxacin activated and degranulated primary human mast cells, but only MRGPRX2-positive and not MRGPRX2-negative or -silenced mast cells. Sugammadex attenuated the atracurium-induced and MRGPRX2-mediated activation and degranulation of human mast cells by reducing free atracurium levels. The mast cells of patients with IgE-independent anaphylaxis to rocuronium were similar, in their MRGPRX2 expression and function, to those of patients with IgE-mediated anaphylaxis. These findings further improve our understanding of the role and relevance of MRGPRX2-driven mast cell activation in anaphylactic reactions to NMBAs and FQs and may help to improve their prediction, prevention, and treatment.
Keywords
