Schnyder Benno, Pichler Werner J
Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
Mayo Clin Proc. 2009 Mar;84(3):268-72. doi: 10.4065/84.3.268.
We identified English-language publications on hypersensitivity reactions to xenobiotics through the PubMed database, using the search terms drug and/or xenobiotic, hypersensitivity reaction, mechanism, and immune mediated. We analyzed articles pertaining to the mechanism and the role of T cells. Immune hypersensitivity reactions to drugs are mediated predominantly by IgE antibodies or T cells. The mechanism of IgE-mediated reactions is well investigated, but the mechanisms of T-cell-mediated drug hypersensitivity are not well understood. The literature describes 2 concepts: the hapten/prohapten concept and the concept of pharmacological interactions of drugs with immune receptors. In T-cell-mediated allergic drug reactions, the specificity of the T-cell receptor that is stimulated by the drug may often be directed to a cross-reactive major histocompatibility complex-peptide compound. Thus, previous contact with the causative drug is not obligatory, and an immune mechanism should be considered as the cause of hypersensitivity, even in reactions that occur on primary exposure. Indeed, immune-mediated reactions to xenobiotics in patients without prior exposure to the agent have been described recently for radiocontrast media and neuromuscular blocking agents. Thus, the "allergenic" potential of a drug under development should be evaluated not only by screening its haptenlike characteristics but also by assessing its direct immunostimulatory potential.
我们通过PubMed数据库，使用搜索词“药物和/或外源性物质”“超敏反应”“机制”和“免疫介导”，识别了关于外源性物质超敏反应的英文出版物。我们分析了与T细胞机制和作用相关的文章。药物免疫超敏反应主要由IgE抗体或T细胞介导。IgE介导反应的机制已得到充分研究，但T细胞介导的药物超敏反应机制尚不清楚。文献描述了两个概念：半抗原/前半抗原概念以及药物与免疫受体的药理相互作用概念。在T细胞介导的过敏性药物反应中，被药物刺激的T细胞受体的特异性可能常常指向一种交叉反应性主要组织相容性复合体-肽复合物。因此，既往接触致病药物并非必需条件，即使在初次接触时发生的反应中，免疫机制也应被视为超敏反应的原因。事实上，最近已报道了在未预先接触造影剂和神经肌肉阻滞剂的患者中发生的对外源性物质的免疫介导反应。因此，正在研发的药物的“致敏”潜力不仅应通过筛选其半抗原样特性来评估，还应通过评估其直接免疫刺激潜力来评估。
