Hausmann Oliver V, Gentinetta Thomas, Bridts Chris H, Ebo Didier G
Department of Allergology, Department of Rheumatology, Allergology and Clinical Immunology, Inselspital, Freiburgstrasse, University of Bern, Bern 3010, Switzerland.
Immunol Allergy Clin North Am. 2009 Aug;29(3):555-66. doi: 10.1016/j.iac.2009.04.011.
Diagnosis of drug allergy involves first the recognition of sometimes unusual symptoms as drug allergy and, second, the identification of the eliciting drug. This is an often difficult task, as the clinical picture and underlying pathomechanisms are heterogeneous. In clinical routine, physicians frequently have to rely upon a suggestive history and eventual provocation tests, both having their specific limitations. For this reason both in vivo (skin tests) and in vitro tests are investigated intensively as tools to identify the disease-eliciting drug. One of the tests evaluated in drug allergy is the basophil activation test (BAT). Basophils with their high-affinity IgE receptors are easily accessible and therefore can be used as indicator cells for IgE-mediated reactions. Upon allergen challenge and cross-linking of membrane-bound IgE antibodies (via Fc-epsilon-RI) basophils up-regulate certain activation markers on their surface such as CD63 and CD203c, as well as intracellular markers (eg, phosphorylated p38MAPK). In BAT, these alterations can be detected rapidly on a single-cell basis by multicolor flow cytometry using specific monoclonal antibodies. Combining this technique with in vitro passive sensitization of donor basophils with patients' serum, one can prove the IgE dependence of a drug reaction. This article summarizes the authors' current experience with the BAT in the diagnostic management of immediate-type drug allergy mediated by drug-specific IgE antibodies.
药物过敏的诊断首先涉及将有时不寻常的症状识别为药物过敏,其次是确定引发过敏的药物。这通常是一项艰巨的任务,因为临床表现和潜在的发病机制是多种多样的。在临床实践中,医生常常不得不依赖提示性病史和最终的激发试验,但这两者都有其特定的局限性。因此,体内试验(皮肤试验)和体外试验都作为识别引发疾病药物的工具而被深入研究。嗜碱性粒细胞活化试验(BAT)是药物过敏中评估的试验之一。嗜碱性粒细胞具有高亲和力的IgE受体,易于获取,因此可作为IgE介导反应的指示细胞。在变应原攻击并使膜结合的IgE抗体(通过Fc-ε-RI)交联后,嗜碱性粒细胞会上调其表面的某些活化标志物,如CD63和CD203c,以及细胞内标志物(如磷酸化的p38MAPK)。在BAT中,使用特异性单克隆抗体通过多色流式细胞术可在单细胞基础上快速检测到这些变化。将该技术与用患者血清对供体嗜碱性粒细胞进行体外被动致敏相结合,可证实药物反应的IgE依赖性。本文总结了作者目前在由药物特异性IgE抗体介导的速发型药物过敏诊断管理中使用BAT的经验。