Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium; Department of Paediatrics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Br J Anaesth. 2020 Dec;125(6):970-975. doi: 10.1016/j.bja.2020.06.024. Epub 2020 Jul 22.
Immediate drug hypersensitivity reactions are an increasing public health issue and a frequent cause of life-threatening anaphylaxis. Conventional confirmatory testing include skin tests and, for a few drugs, quantification of drug-specific immunoglobulin E (IgE) antibodies. However, none of these tests are absolutely predictive for the clinical outcome, and can yield false-negative and false-positive results. We performed a proof-of-concept study to assess whether a mast cell activation test could improve diagnosis of IgE-mediated chlorhexidine hypersensitivity, a common cause of perioperative anaphylaxis.
Human mast cells were generated from CD34 progenitor cells and sensitised with patients' sera to become IgE+ human mast cells (dMC), and then incubated with chlorhexidine to assess degranulation. We compared the diagnostic performance of this mast cell activation test with serum from patients with and without positive skin test and basophil activation test to chlorhexidine.
In dMC sensitised with sera from patients with a positive skin test and basophil activation test to chlorhexidine showed drug-specific and concentration-dependent degranulation upon stimulation with chlorhexidine, determined by surface upregulation of the degranulation marker CD63. In contrast, dMC sensitised with sera from patients with a negative skin test and basophil activation test to chlorhexidine were unresponsive in the mast cell activation test.
Our study suggests that the mast cell activation test can be used to diagnose IgE/FcεRI-dependent immediate drug hypersensitivity reactions. It also shows potential to assess the clinical relevance of drug-specific IgE antibodies in their ability to elicit mast cell degranulation, and therefore discriminate between allergy and sensitisation. Extended studies are required to verify whether this technique can be used in other causes of perioperative anaphylaxis.
速发型药物过敏反应是一个日益严重的公共卫生问题，也是导致危及生命的过敏反应的常见原因。传统的确认性检测包括皮肤试验，以及对于少数药物，定量检测药物特异性免疫球蛋白 E（IgE）抗体。然而，这些检测都不能绝对预测临床结果，并且可能产生假阴性和假阳性结果。我们进行了一项概念验证研究，以评估肥大细胞活化试验是否可以改善对 IgE 介导的洗必泰过敏的诊断，洗必泰是围手术期过敏反应的常见原因。
用人 CD34 祖细胞生成肥大细胞，并将患者的血清致敏以成为 IgE+人肥大细胞（dMC），然后用洗必泰来孵育以评估脱颗粒。我们比较了这种肥大细胞活化试验与对洗必泰具有阳性皮肤试验和嗜碱性粒细胞活化试验的患者血清的诊断性能。
在 dMC 中，用对洗必泰具有阳性皮肤试验和嗜碱性粒细胞活化试验的患者血清致敏的细胞在受到洗必泰刺激时表现出药物特异性和浓度依赖性脱颗粒，通过脱颗粒标志物 CD63 的表面上调来确定。相比之下，用对洗必泰具有阴性皮肤试验和嗜碱性粒细胞活化试验的患者血清致敏的 dMC 在肥大细胞活化试验中无反应。
我们的研究表明，肥大细胞活化试验可用于诊断 IgE/FcεRI 依赖性即刻药物过敏反应。它还显示出评估药物特异性 IgE 抗体在引发肥大细胞脱颗粒方面的临床相关性的潜力，从而区分过敏和致敏。需要进行扩展研究以验证该技术是否可用于其他围手术期过敏反应的原因。
