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J Investig Allergol Clin Immunol 2019; Vol. 29(5): 401-402 © 2019 Esmon Publicidad
doi: 10.18176/jiaci.0416
LETTERS TO THE EDITOR
Basophil Activation Test in Amiodarone
Hypersensitivity and Non–IgE-Mediated Allergy
Vella A1, Bjørklund G2, Chirumbolo S2,3
1AOUI –University Hospital, Section of Immunology, Verona, Italy
2Council for Nutritional and Environmental Medicine (CONEM),
Mo i Rana, Norway
3Department of Neurosciences, Biomedicine and Movement
Sciences, University of Verona, Verona, Italy
J Investig Allergol Clin Immunol 2019; Vol. 29(5): 401-402
doi: 10.18176/jiaci.0416
Key words: Basophil activation test. CD63. CD203c. Amiodarone.
Palabras clave: Test de activación de basófilos. CD63. CD203c.
Amiodarona.
To the Editor:
The recent article by Sánchez et al [1] investigated the
fundamental role played by the application of a basophil
phenotyping protocol including the CD123 and HLA-DR
markers for electronically capturing cells in flow cytometry.
The authors described 2 cases of immediate hypersensitivity
to amiodarone that were successfully diagnosed using a
CD123pos/HLA-DRneg gating protocol, with CD63 as the
activation marker. Interestingly, the authors reported an
increase in the CD63 percentage in peripheral blood samples
treated with amiodarone 0.2 mg/mL, although the activation
did not appear to follow a dose-response relationship. In the
case of a purported anaphylactic reaction, CD63 upregulation
increased by 37% (stimulation index, 5.11 [≥3]), while in the
84-year-old patient with no apparent allergy background but
who was treated with antihistamine and corticosteroid therapy
for itching and a red rash 15 minutes after taking amiodarone,
CD63 upregulation reached 60% with a stimulation index of
30 [1]. The merit of this paper is that it shows the ability of
the basophil activation test (BAT) to detect an allergic episode
very early and to prevent the adverse effects associated with
a skin prick test. We expected to observe a more pronounced
CD63 response in the case of anaphylaxis in the 48-year-old
patient, who also responded to the lowest doses of amiodarone
(0.1 mg/mL), with a CD63 percentage of 14%-15%, while the
second patient did not. Notwithstanding, the findings led to
us raise some questions.
Basophils express A1 adenosine receptors, which are
targeted by amiodarone [2,3]. The rapid up-regulation of the
tetraspanin LAMP3, ie, CD63, is associated with a type of
degranulation known as anaphylactic degranulation, which
is also the mode used by a non–IgE-mediated basophil
response (as occurs for fMLP) some seconds after piecemeal
degranulation [4]. Therefore, in the patient with the higher
stimulation index for CD63, we may describe the event as
a “threshold” effect of the amiodarone-mediated action on
basophil A1 purinergic receptors, while for the anaphylactic
patient we cannot exclude a real hypersensitivity mechanism.
In these circumstances, as the phenotyping protocol is based
on a panel of markers that excludes CD203c, the authors
should select CD203c to determine whether their finding can
be explained by a non–IgE-mediated mechanism [5]. It is well
known that adenosine receptors in basophils downregulate
cellular activation expressed via histamine release and the
degranulation event, and it can be suggested that amiodarone,
which dampens the sensitivity of A1 adenosine receptors,
rapidly increases the anaphylactic degranulation mechanism
of CD63 upregulation, resulting in the considerable CD63
percentage observed by the authors [1-3]. This speculation
of ours seems to find some support in the evidence that
the 84-year-old woman did not have a history of allergy to
amiodarone. In the case of the 48-year-old man, however, who
was clearly allergic to amiodarone, there was a dose-dependent
increase in the CD63 percentage [1], with no threshold effects
caused by mechanisms of receptor binding and recycling at
some distance from the FcεRI/IgEs signaling pathway.
In conclusion, we would like to propose that the use of a
BAT with a CD45dim /CD123high /HLA-DRneg/CD63pos protocol
makes it possible to introduce 2 activation markers, ie, CD63
and CD203c, which may enable us to discriminate between
an IgE-mediated response and a non–IgE-mediated response.
In this paper, BAT emerges as a worthy tool for diagnosis of
hypersensitivity and non–IgE-dependent immune responses
to drugs. It should certainly be considered an essential tool
in allergy diagnosis.
Funding
The authors declare that no funding was received for the
present study.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
References
1. Vílchez Sánchez F, Lluch Bernal M, González Muñoz M,
Marques Mejías MA, Quirce Gancedo S, Cabañas Moreno
R. Usefulness of basophil activation test in the diagnosis of
amiodarone hypersensitivity. J Investig Allergol Clin Immunol.
2019 Apr 24:0. doi: 10.18176/jiaci.0404.
2. Marone G, Findlay SR, Lichtenstein LM. Adenosine receptor
on human basophils: modulation of histamine release. J
Immunol. 1979 Oct;123(4):1473-7.