Rocuronium Hypersensitivity: Does Off-Target Occupation of the MRGPRX2 Receptor Play a Role?

Abstract

BACKGROUND:

The neuromuscular blocking agent (NMBA) rocuronium is a relevant cause of perioperative hypersensitivity (POH) with a significant risk of diagnostic error. Recently, it has been suggested to reclassify hypersensitivity to NMBA as type A reactions resulting from off-target occupation of the nonimmune MRGPRX2 receptor.

OBJECTIVE:

To investigate whether basophil activation experiments can benefit diagnosis and add to the insights in the pathomechanisms of rocuronium hypersensitivity.

METHODS:

A total of 140 patients with a suspected POH to rocuronium in whom peak tryptase was available had complete diagnostic workup for all potential culprits including triple confirmatory testing with skin tests, basophil activation test (BAT), and quantification of specific IgE (sIgE) antibodies to rocuronium and morphine. To further analyze the clinical relevance of sIgE antibodies, quantitative basophil inhibition experiments were performed by coincubation of the cells with rocuronium and morphine, an opiate known to harbor a substituted ammonium structure.

RESULTS:

Diagnosis of rocuronium hypersensitivity was established in 72 of 140 patients (51.4%), of whom 65 (90.3%) demonstrated mast cell activation. Of the 72 patients, 64 displayed a positive skin test, 8 (11.1%) had their diagnosis documented only by BAT. Coincubation of morphine and rocuronium induced a dose-dependent inhibition of BAT with rocuronium that was restricted to 4 of 6 patients with IgE reactivity to rocuronium and/or morphine.

CONCLUSIONS:

BAT can benefit diagnosis of rocuronium hypersensitivity. As basophils barely express MRGPRX2 and BAT rocuronium can be inhibited by morphine, we believe that hypersensitivity to rocuronium still mainly results from IgE/high-affinity receptor for sIgE (FcεRI)-dependent effector cell activation. However, it cannot be excluded that in a few patients rocuronium hypersensitivity results from off-target occupation of the MRGPRX2 receptor.

• Authors: Athina L Van Gasse, Jessy Elst, Chris H Bridts, Christel Mertens, Margaretha Faber, Margo M Hagendorens, Luc S De Clerck, Vito Sabato, Didier G Ebo
• Journal: The journal of allergy and clinical immunology. In practice (J Allergy Clin Immunol Pract) Vol. 7 Issue 3 Pg. 998-1003 (03 2019) ISSN: 2213-2201 [Electronic] United States
• PMID: 30315997 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• MRGPRX2 protein, human
• Nerve Tissue Proteins
• Neuromuscular Nondepolarizing Agents
• Receptors, G-Protein-Coupled
• Receptors, Neuropeptide
• Immunoglobulin E
• Rocuronium

Topics

• Adult
• Aged
• Basophil Degranulation Test
• Drug Hypersensitivity (diagnosis, immunology, metabolism)
• Female
• Humans
• Immunoglobulin E (immunology)
• Male
• Mast Cells (immunology)
• Middle Aged
• Nerve Tissue Proteins (metabolism)
• Neuromuscular Nondepolarizing Agents (adverse effects)
• Receptors, G-Protein-Coupled (metabolism)
• Receptors, Neuropeptide (metabolism)
• Rocuronium (adverse effects)
• Skin Tests
• Young Adult