Abstract
AbstractThe study of anaphylactoid reactions during perioperative procedures
and anaesthesia represents a diagnostic challenge for allergists, as many drugs are
administered simultaneously, and approximately half of them trigger allergic
reactions without a verifiable IgE-mediated mechanism. Recently, mast cell receptor
MRGPRX2 has been identified as a cause of pseudo-allergic drug reactions. In this
study, we analyse the ability of certain drugs used during perioperative procedures
and anaesthesia to induce MRGPRX2-dependent degranulation in human mast cells and
sera from patients who experienced an anaphylactoid reaction during the
perioperative procedure. Using a β-hexosaminidase release assay, several drugs were
seen to cause mast cell degranulation in vitro in
comparison with unstimulated cells, but only morphine, vancomycin and cisatracurium
specifically triggered this receptor, as assessed by the release of β-hexosaminidase
in the control versus the MRGPRX2-silenced cells. The same outcome was seen when
measuring degranulation based on the percentage of CD63 expression at identical
doses. Unlike that of the healthy controls, the sera of patients who had experienced
an anaphylactoid reaction induced mast-cell degranulation. The degranulation ability
of these sera decreased when MRGPRX2 was silenced. In conclusion, MRGPRX2 is a
candidate for consideration in non-IgE-mediated allergic reactions to some
perioperative drugs, reinforcing its role in mast cell responses and their
pathophysiology.
Publisher
Springer Science and Business Media LLC
Reference26 articles.
1. Berroa, F. et al. The usefulness
of plasma histamine and different tryptase cut-off points in the diagnosis of
peranaesthetic hypersensitivity reactions. Clin Exp
Allergy
44, 270–277, https://doi.org/10.1111/cea.12237 (2014).
2. Bousquet, P. J. et al.
Provocation tests in diagnosing drug hypersensitivity. Curr Pharm Des
14, 2792–2802 (2008).
3. Mertes, P. M. et al. Reducing
the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical
practice. J Investig Allergol Clin Immunol
21, 442–453 (2011).
4. Subramanian, H., Gupta, K. & Ali, H. Roles of Mas-related G
protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic
drug reactions, and chronic inflammatory diseases. J
Allergy Clin Immunol
138, 700–710, https://doi.org/10.1016/j.jaci.2016.04.051 (2016).
5. McNeil, B. D. et al.
Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug
reactions. Nature
519, 237–241, https://doi.org/10.1038/nature14022 (2015).
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