Serum MRGPRX2 as a long-time available biomarker for
drug-induced anaphylaxis
To the Editor,
The diagnosis of anaphylaxis is based on clinical symptoms after
exposure to a trigger factor1. Serum tryptase is
useful for an accurate diagnosis of anaphylaxis. However, one of its
limitations is short half-life, hence the need for blood samples to be
obtained at the onset of anaphylaxis2,3. Mas-related G
protein-coupled receptor-X2 (MRGPRX2), expressed in mast cells, is
related to degranulation of mast cells in the IgE-independent pathway
for anaphylaxis4-6. We aimed to evaluate serum MRGPRX2
levels in patients with drug-induced anaphylaxis (DIA) and to determine
usefulness as a potential marker of anaphylaxis by maintaining its
concentrations longer.
We included 68 patients who consulted at allergy clinic for a history of
anaphylaxis after causal drug administration between January 2010 and
December 2017. Diagnosis of DIA and causal drugs were determined by an
allergist. Patients were excluded if 1) causal drugs were ambiguous, or
2) other relevant causes were combined. Each patient underwent serum
MRGPRX2 level measurement randomly at least once from the onset of
anaphylaxis. MRGPRX2 levels were determined using an ELISA kit from
MyBioSource. We also measured MRGPRX2 levels of 74 controls.
We classified DIA patients according to causal drugs to investigate the
difference in MRGPRX2 levels between drugs. In addition, we analyzed the
MRGPRX2 levels according to the time interval from the anaphylactic
event to verify maintenance of MRGPRX2 levels over a longer period of
time. The time interval for each patient was defined as the gap between
the measurement time of MRGPRX2 levels and the anaphylactic event. This
study was approved by the institutional review board of Asan Medical
Center (2018-1252), and subjects provided written informed consent.
This study included 74 controls and 68 patients with DIA. The mean
MRGPRX2 level in the DIA group was significantly higher than that of the
control group (57.4±42.8 vs. 17.5±12.7, p <.001)
(Figure 1A). Patients were classified into 5 subgroups according to
their causal drugs, including antibiotics, non-steroidal
anti-inflammatory drugs (NSAIDs), histamine-2 receptor blockers (H2-
blockers), radiocontrast media (RCM), and others. The others included
clopidogrel, proton pump inhibitors, diltiazem, carboplatin, rifampicin,
and ethambutol. The most common causal drug was antibiotics (49%),
followed by NSAIDs (19%), and H2 blockers (10%). The mean MRGPRX2
levels in patients with DIA caused by antibiotics were higher than in
those with other subgroups, but there was no significant difference
between the 5 causal drugs (p = 0.964) (Table 1).
MRGPRX2 levels of patients with 4–5week time interval were higher
(97.4±39.7) than those with 0–1 week (51.9±45.2), 1–2 weeks
(54.0±42.1), 2–3 weeks (66.9±39.7), and 3–4 weeks (47.2±27.6) but with
no significant difference (p = 0.099) (Table 1). Overall, mean
MRGPRX2 levels in each time interval were higher than those in the
controls (Figure 1B). There was no significant difference among the
frequencies of the causal drugs in each time interval (Table S1).
This study demonstrated that serum MRGPRX2 was a potential long-time
biomarker for DIA, maintaining high concentration for more than a month
from the onset of anaphylaxis. Patients with DIA had higher mean MRGPRX2
levels than controls in all time intervals from the anaphylaxis onset.
Thus, MRGPRX2 may be a promising biomarker for supporting a diagnosis of
DIA over a longer period than tryptase.
This study has limitations in that there was no data of serial changes
in MRGPRX2 concentration according to the time interval in the same
patient and no direct comparison between MRGPRX2 and tryptase levels.
However, this is a pilot study. The performance of MRGPRX2 as a useful
biomarker of DIA needs to be further studied using a larger population
and in a longer time.