Role of MicroRNAs in Allergy and Basophil Activation Test for IgE-Mediated Drug Allergy

In this month's editorial, the Editors of the journal have highlighted two fascinating studies that are included in this issue. The first article provides evidence that miR-107 is involved in the allergic response to house dust mites (HDM) in children with asthma [1]. Allergic asthma (AA) is a prevalent phenotype of asthma that presents atopic sensitisations in asthma patients exposed to allergens [2, 3]. Some, but not all, studies have suggested a possible increase in AA over time [4]. HDM are a significant trigger for AA in many regions, with HDM sensitisation potentially leading to severe, and in some instances, life-threatening asthma symptoms. In the study by Kim et al. [1], the relationship between microRNAs (miRNAs) and HDM sensitisation in children with asthma was investigated. The researchers examined serum samples from 1126 children in the Genetics of Asthma in Costa Rica Study (GACRS) and also replicated their findings in the Childhood Asthma Management Program (CAMP). Initially, the study revealed that 17 miRNAs were differentially expressed between HDM-sensitised and non-sensitised children in the GACRS group. Of the 17, miR-642a, let-7c-5p and miR-107 showed the strongest association with HDM sensitisation. Moreover, the CAMP cohort successfully replicated the elevated expression of miR-107 in HDM-sensitised children. Additional mediation analysis also presented significant effects of miR-107 on eosinophil count and total IgE after HDM sensitisation. These findings suggest new insights into the molecular mechanisms underlying HDM sensitisation in paediatric asthma and emphasise the potential of miRNAs, particularly, miR-107, which can be studied further for application as biomarkers or therapeutic targets for AA (Figure 1).

This issue's second editor's choice article reports on the optimisation of the basophil activation assay for identifying IgE-mediated drug allergies [5]. Diagnosing drug allergies is a complex and nuanced process that presents several challenges. Allergic reactions can manifest with a broad spectrum of clinical symptoms, ranging from mild rashes to life-threatening anaphylaxis, making it difficult to establish consistent diagnostic criteria. Reactions may occur immediately or be delayed, sometimes appearing days after exposure [6]. This variability complicates the temporal connection between drug intake and allergic symptoms. Additionally, patients may experience allergic reactions to drug molecules with similar structures, further complicating the identification of the exact trigger, especially in cases involving structurally similar drugs. Unlike testing for environmental allergens, there are limited standardised and clinically validated laboratory tests available for many drug allergies. The reliability and availability of tests like the Basophil Activation Test (BAT) can vary for different drugs [7, 8]. While oral drug provocation tests are considered the gold standard for diagnosis, they carry risks, as they involve administering the suspected allergen to the patient, which could potentially trigger serious allergic reactions. Although IgE-mediated reactions can sometimes be confirmed through skin tests and specific IgE blood tests, non-IgE-mediated drug allergies may lack reliable laboratory markers, making diagnosis largely dependent on clinical history. Clinicians typically rely on a combination of clinical evaluation, patient history, available laboratory tests, and, if deemed safe, challenge tests to arrive at a diagnosis. Given these complexities, diagnosing drug allergies often requires specialised consultation and expert evaluation [9].

In this issue, Alvarez-Arango et al. [5] present a study focused on optimising the basophil passive sensitisation assay and creating practical guidelines by exploring key variable interactions. Flow cytometry was used to analyse open and occupied FcεRI receptors before and after the dissociation of surface-bound sIgE. Basophils were sensitised with serial concentrations of penicillin (BPO)-sIgE in serum or buffer and then incubated for 1, 4 and 18 h, with or without D2O and/or IL-3. Basophil sensitivity was assessed by evaluating FcεRI receptor densities, the ratios of sIgE to total IgE (tIgE), responses to BPO(21)-HSA, and the effects of D2O and/or IL-3. Maximal responses were determined using anti-IgE human antibodies. These optimised conditions were then tested with sera containing peanut sIgE and cat sIgE. This study introduces a method for assessing basophil sensitisation, highlighting the minimum sIgE/tIgE ratio required for effective basophil activation. It takes into consideration critical factors such as the presence of open or unoccupied FcεRI receptors, variations in sIgE/tIgE ratios, and the impact of D2O and IL-3. This method lays a strong foundation for the enhancement and advancement of functional assays related to basophil activation, contributing valuable insights to the allergy and immunology speciality (Figure 2).

M. H. Shamji led development of this manuscript. R. J. Boyle approved the final version of the manuscript.

The authors declare no conflicts of interest.