Osman Ozan Yegit, Metin Yusuf Gelmez, Semra Demir, Nilgun Akdeniz, Ilkim Deniz Toprak, Pelin Karadag, Ali Can, Derya Unal, Gunnur Deniz, Asli Gelincik
{"title":"Diagnosis of ciprofloxacin hypersensitivity improves by incorporating MRGPRX2 in basophil activation test.","authors":"Osman Ozan Yegit, Metin Yusuf Gelmez, Semra Demir, Nilgun Akdeniz, Ilkim Deniz Toprak, Pelin Karadag, Ali Can, Derya Unal, Gunnur Deniz, Asli Gelincik","doi":"10.2500/aap.2025.46.250024","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> Immediate hypersensitivity reactions (IHR) to ciprofloxacin can be caused by Mas-related G-protein coupled receptor X2 (MRGPRX2) as well as immunoglobulin E (IgE)-dependent mechanisms. When considering the complexity of the Patho mechanism, there are doubts with regard to the adequacy of conventional basophil activation test (BAT) in diagnosing fluoroquinolone-induced IHR. Our aim was to present a BAT method that relies on specifically evaluating the basophils expressing MRGPRX2 to increase the diagnosis rate of ciprofloxacin-induced MRGPRX2-mediated IHR. <b>Methods:</b> CD63 and MRGPRX2 expressions were analyzed with and without ciprofloxacin stimulation on basophils from patients and healthy controls by using flow cytometry. The net percentage of upregulation (net%) of MRGPRX2 and CD63 on basophils were statistically analyzed. <b>Results:</b> Fourteen patients with confirmed IHR to ciprofloxacin and age- and gender-matched 12 healthy controls were analyzed. The median (interquartile range) age of the patients was 39.5 years (33.5-51.5 years) and 92.9% were women. The median (interquartile range) net% expression of CD63 on basophils, MRGPRX2 on basophils, and CD63 on MRGPRX2<sup>+</sup> basophils after ciprofloxacin stimulation was all higher in patients (18.1 [5.8-25.3], 3.7 [3.0-5.4], and 13.9 [7.8-28.8], respectively) compared with healthy controls (6.6 [3.8-11.4], 2.4 [0.6-3.7], and 1.3 [0.4-8.9], respectively) (p = 0.027, p = 0.042, and p = 0.001, respectively). Receiver operating characteristic analysis showed that the net% of CD63 expression on MRGPRX2<sup>+</sup> basophils had a greater area under the curve to predict ciprofloxacin IHR than did the net% of CD63 expression on basophils. A net% > 10.3% of CD63 expression on basophils showed a sensitivity of 71.4% and a specificity of 75.0%, whereas a net% > 3.9% of theCD63 expression on MRGPRX2<sup>+</sup> basophils showed a sensitivity of 100% and a specificity of 75.0%. The proposed method diagnosed four more patients compared with the conventional BAT. <b>Conclusion:</b> Analysis of our data indicated that the determination of MRGPRX2 together with CD63 in basophils improves the <i>in vitro</i> diagnosis of ciprofloxacin IHR with a better sensitivity compared with conventional BAT.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"247-256"},"PeriodicalIF":2.6000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergy and asthma proceedings","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2500/aap.2025.46.250024","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Immediate hypersensitivity reactions (IHR) to ciprofloxacin can be caused by Mas-related G-protein coupled receptor X2 (MRGPRX2) as well as immunoglobulin E (IgE)-dependent mechanisms. When considering the complexity of the Patho mechanism, there are doubts with regard to the adequacy of conventional basophil activation test (BAT) in diagnosing fluoroquinolone-induced IHR. Our aim was to present a BAT method that relies on specifically evaluating the basophils expressing MRGPRX2 to increase the diagnosis rate of ciprofloxacin-induced MRGPRX2-mediated IHR. Methods: CD63 and MRGPRX2 expressions were analyzed with and without ciprofloxacin stimulation on basophils from patients and healthy controls by using flow cytometry. The net percentage of upregulation (net%) of MRGPRX2 and CD63 on basophils were statistically analyzed. Results: Fourteen patients with confirmed IHR to ciprofloxacin and age- and gender-matched 12 healthy controls were analyzed. The median (interquartile range) age of the patients was 39.5 years (33.5-51.5 years) and 92.9% were women. The median (interquartile range) net% expression of CD63 on basophils, MRGPRX2 on basophils, and CD63 on MRGPRX2+ basophils after ciprofloxacin stimulation was all higher in patients (18.1 [5.8-25.3], 3.7 [3.0-5.4], and 13.9 [7.8-28.8], respectively) compared with healthy controls (6.6 [3.8-11.4], 2.4 [0.6-3.7], and 1.3 [0.4-8.9], respectively) (p = 0.027, p = 0.042, and p = 0.001, respectively). Receiver operating characteristic analysis showed that the net% of CD63 expression on MRGPRX2+ basophils had a greater area under the curve to predict ciprofloxacin IHR than did the net% of CD63 expression on basophils. A net% > 10.3% of CD63 expression on basophils showed a sensitivity of 71.4% and a specificity of 75.0%, whereas a net% > 3.9% of theCD63 expression on MRGPRX2+ basophils showed a sensitivity of 100% and a specificity of 75.0%. The proposed method diagnosed four more patients compared with the conventional BAT. Conclusion: Analysis of our data indicated that the determination of MRGPRX2 together with CD63 in basophils improves the in vitro diagnosis of ciprofloxacin IHR with a better sensitivity compared with conventional BAT.
期刊介绍:
Allergy & Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists. The goal of the Proceedings is to publish articles with a predominantly clinical focus which directly impact quality of care for patients with allergic disease and asthma. Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. Published material includes peer-reviewed original research, clinical trials and review articles.