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首页> 外文期刊>Clinical and Translational Allergy >Evaluation of immediate allergic reactions to dipyrone using dipyrone metabolites in basophil activation test
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Evaluation of immediate allergic reactions to dipyrone using dipyrone metabolites in basophil activation test

机译：在嗜碱性粒细胞活化试验中使用双嘧啶代谢物评估对双嘧啶的立即过敏反应

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BackgroundImmediate selective hypersensitivity reactions to pyrazolonesare thought to be mediated by specific-IgE antibodies.The diagnosis of selective reactions to pyrazolonesis mainly based on the clinical history, skin testing and/or drug provocation test (DPT). Skin testing has lowsensitivity and has potential risk of eliciting an anaphylacticresponse as well as DPT. Therefore the use of invitro tests could be a safe and straightforward approach,although till now no well-validated test is available.Basophil activation test (BAT) has been proposed as anew in vitro diagnostic tool for different drug reactionsalthough its sensibility is not optimal. The aim of thisstudy was to analyze the potential usefulness of dipyronemetabolites to improve BAT sensitivity.MethodsThe study included a group of 8 patients with a selectiveimmediate hypersensitivity reaction to dipyrone, plus agroup of 15 non-atopic controls tolerating dipyrone. BATwas done with dipyrone and four metabolites purifiedfrom human urine samples (4-methylamino antipyrine(MAA), 4-aminoantipyrine (AA), 4-acetylamino antipyrine(AAA) and 4-formylamino antipyrine (FAA). To confirmIgE-mediated basophil activation, the phosphatidylinositol3-kinase (PI3-K) inhibitor wortmannin (WTM) was usedin the BAT.ResultsAll patients were skin test positive in the immediate readingto dipyrone and had good tolerance to acetyl salicylicacid in drug provocation test. BAT results were positivein 2 patients to both dipyrone and MAA, in 2 patients toMAA alone and in 1 patient to AA alone. We confirmedthat positive BAT results were an IgE-mediated responseby using the WTM. All healthy controls showed negativeBAT to dipyrone and metabolites.ConclusionsThis study demonstrates the role of dipyrone metabolites inimmediate reactions and supports the hypothesis that drugmetabolites may underlie some allergic reactions. The additionaluse of dipyrone metabolites, besides the parent drug,increases BAT sensitivity, thus improving and refining theBAT-based diagnosis of selective reactions to dipyrone.These results deserve further studies using a higher numberof patients and other dipyrone metabolites to gain deeperinsight in the potential use of metabolite-based BAT as atarget biomarker for allergic reactions to dipyrone.
机译：背景技术对吡唑啉酮的选择性超敏反应被认为是由特异性IgE抗体介导的。对吡唑啉酮症选择性反应的诊断主要基于临床病史，皮肤试验和/或药物激发试验（DPT）。皮肤测试的敏感性较低，并且具有引起过敏反应和DPT的潜在风险。因此，尽管到目前为止尚无经过充分验证的测试，但体外测试的使用可能是一种安全，简单的方法。嗜碱性粒细胞活化测试（BAT）已被提议作为一种针对不同药物反应的新型体外诊断工具，尽管其敏感性并非最佳。本研究的目的是分析双嘧达隆代谢物对提高BAT敏感性的潜在作用。方法该研究包括8名对双嘧达隆具有选择性立即超敏反应的患者，以及15名耐受双嘧达隆的非异位对照。使用双嘧啶和从人尿液样品中纯化的四种代谢物（4-甲基氨基安替比林（MAA），4-氨基安替比林（AA），4-乙酰基氨基安替比林（AAA）和4-甲酰基氨基安替比林（FAA））进行了BAT验证。IgE介导的嗜碱性粒细胞活化，结果在BAT中使用磷脂酰肌醇3-激酶（PI3-K）抑制剂渥曼青霉素（WTM）。所有患者在对双嘧啶的即时读数中皮肤试验均为阳性，并且对药物水杨酸的乙酰水杨酸耐受性良好，在2例患者中BAT均为阳性结论：双嘧啶和MAA在单独使用MAA的2例患者和单独使用AA的1例患者中均得到证实，我们证实，WTM是IgE介导的BAT反应阳性，所有健康对照组对双嘧啶和代谢产物均呈阴性BAT。立即反应并支持以下假设：药物代谢物可能是某些过敏反应的基础。地毯提高了BAT的敏感性，从而改善和完善了基于BAT的对双嘧啶选择性反应的诊断。这些结果值得进一步研究，使用更多的患者和其他双嘧啶代谢物，以深入了解基于代谢物的BAT作为目标生物标志物的潜在用途对潘生酮有过敏反应。

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