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.