Principles, potential, and limitations of ex vivo basophil activation by flow cytometry in allergology: A narrative review

Ebo, Didier G.; Bridts, Chris H.; Mertens, Christel; Sabato, Vito

doi:10.1016/j.jaci.2020.10.027

Cited by 52 publications

(44 citation statements)

References 146 publications

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“…Exclusion of other mechanisms, i.e. IgE-mediated activation, by sIgE and BAT is the best approach to identifying patients with probably MRGPRX2-dependent reactions ( 16 , 28 ). Unlike MCs, resting circulation basophils barely express MRGPRX2 ( 29 , 30 ) and have repeatedly been shown not to respond in a non-specific manner to potent MRGPRX2 agonists such as opiates (e.g.…”

Section: Discussionmentioning

confidence: 99%

Novel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Novel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones

et al. 2021

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“…g Although BATs can be performed up to 24 h after sampling, it is recommended to perform analysis within 4 h after collection. 2 In contrast, patients' sera or plasma that are used in the pMAT can easily be stored and shipped and thereby enable deferred analyses. h pMAT allows simultaneous testing of several patients' sera or plasma using the same MC line or donor MC culture.…”

Section: Key Messagesmentioning

confidence: 99%

“…The clinical utility of the BAT in the diagnosis and monitoring of allergic diseases has widely been studied and reviewed. 1,2 These studies and reviews show that the BAT, although offering many advantages over mediator release tests, is left with some weaknesses that hinder a wider application. Although the BAT can be executed up to 24 h of collection, 3 it is preferable to perform the analyses within 4 h 4 and the technique does not advance diagnosis in patients with non-responsive cells.…”

Section: Introductionmentioning

confidence: 99%

Mast cell activation tests by flow cytometry: A new diagnostic asset?

Elst

Poorten

Gasse

et al. 2021

Clin Experimental Allergy

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Since the late nineties, evidence has accumulated that flow-assisted basophil activation test (BAT) might be an accessible and reliable method to explore the mechanisms governing basophil degranulation and diagnostic allowing correct prediction of the clinical outcome following exposure to the offending allergen(s) and cross-reactive structures for different IgE-dependent allergies and particular forms of autoimmune urticaria. Although the BAT offers many advantages over mediator release tests, it is left with some weaknesses that hinder a wider application. It is preferable to perform the BAT analysis within 4 h of collection, and the technique does not advance diagnosis in patients with non-responsive cells. Besides, the BAT is difficult to standardize mainly because of the difficulty to perform large batch analyses that might span over several days. This article reviews the status of flow cytometric mast cell activation test (MAT) using passively sensitized mast cells (MCs) with patients' sera or plasma (henceforth indicated as passive MAT; pMAT) using both MC lines and cultured MCs in the diagnosis of IgE-dependent allergies. In addition, this paper provides guidance for generating human MCs from peripheral blood CD34 + progenitor cells (PBCMCs) and correct interpretation of flow cytometric analyses of activated and/or degranulating cells. With the recent recognition of the mas-related G protein-coupled receptor X2 (MRGPRX2) occupation as a putative mechanism of immediate drug hypersensitivity reactions (IDHRs), we also speculate how direct activation of MCs (dMAT)-that

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“…Few studies have applied skin prick tests, which may give false positive/negative results due to the different exposure routes. As for the ex vivo basophil activation test (BAT), the detection sensitivity also decreases over time [ 131 ]. In addition, recent studies have primarily focused on the major fish allergen, i.e., parvalbumin.…”

Section: Effect Of Processing On Fish Allergensmentioning

confidence: 99%

Effect of Processing on Fish Protein Antigenicity and Allergenicity

Jiang

Rao

2021

Foods

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Fish allergy is a life-long food allergy whose prevalence is affected by many demographic factors. Currently, there is no cure for fish allergy, which can only be managed by strict avoidance of fish in the diet. According to the WHO/IUIS Allergen Nomenclature Sub-Committee, 12 fish proteins are recognized as allergens. Different processing (thermal and non-thermal) techniques are applied to fish and fishery products to reduce microorganisms, extend shelf life, and alter organoleptic/nutritional properties. In this concise review, the development of a consistent terminology for studying food protein immunogenicity, antigenicity, and allergenicity is proposed. It also summarizes that food processing may lead to a decrease, no change, or even increase in fish antigenicity and allergenicity due to the change of protein solubility, protein denaturation, and the modification of linear or conformational epitopes. Recent studies investigated the effect of processing on fish antigenicity/allergenicity and were mainly conducted on commonly consumed fish species and major fish allergens using in vitro methods. Future research areas such as novel fish species/allergens and ex vivo/in vivo evaluation methods would convey a comprehensive view of the relationship between processing and fish allergy.

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Principles, potential, and limitations of ex vivo basophil activation by flow cytometry in allergology: A narrative review

Cited by 52 publications

References 146 publications

Novel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones

Novel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones

Mast cell activation tests by flow cytometry: A new diagnostic asset?

Effect of Processing on Fish Protein Antigenicity and Allergenicity

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