ADR-AC, Bern, Switzerland.
Allergy. 2022 Feb;77(2):404-415. doi: 10.1111/all.14962. Epub 2021 Jun 14.
Drug hypersensitivity reactions (DHR) are heterogeneous and unusual immune reactions with rather unique clinical presentations. Accumulating evidence indicates that certain non-covalent drug-protein interactions are able to elicit exclusively effector functions of antibody reactions or complete T-cell reactions which contribute substantially to DHR. Here, we discuss three key interactions; (a) mimicry: whereby soluble, non-covalent drug-protein complexes ("fake antigens") mimic covalent drug-protein adducts; (b) increased antibody affinity: for example, in quinine-type immune thrombocytopenia where the drug gets trapped between antibody and membrane-bound glycoprotein; and (c) p-i-stimulation: where naïve and memory T cells are activated by direct binding of drugs to the human leukocyte antigen and/or T-cell receptors. This transient drug-immune receptor interaction initiates a polyclonal T-cell response with mild-to-severe DHR symptoms. Notable complications arising from p-i DHR can include viral reactivations, autoimmunity, and multiple drug hypersensitivity. In conclusion, DHR is characterized by abnormal immune stimulation driven by non-covalent drug-protein interactions. This contrasts DHR from "normal" immunity, which relies on antigen-formation by covalent hapten-protein adducts and predominantly results in asymptomatic immunity.
药物超敏反应 (DHR) 是一种异质性和不常见的免疫反应，具有相当独特的临床特征。越来越多的证据表明，某些非共价药物-蛋白相互作用能够引发仅抗体反应的效应功能或完整的 T 细胞反应，这对 DHR 有很大贡献。在这里，我们讨论三个关键的相互作用；(a)模拟：可溶性非共价药物-蛋白复合物（“假抗原”）模拟共价药物-蛋白加合物；(b)抗体亲和力增加：例如，在奎宁型免疫性血小板减少症中，药物被困在抗体和膜结合糖蛋白之间；(c) p-i 刺激：幼稚和记忆 T 细胞通过药物与人类白细胞抗原和/或 T 细胞受体的直接结合而被激活。这种短暂的药物-免疫受体相互作用引发了多克隆 T 细胞反应，伴有轻度至重度 DHR 症状。p-i DHR 引起的显著并发症包括病毒再激活、自身免疫和多种药物超敏反应。总之，DHR 的特征是由非共价药物-蛋白相互作用驱动的异常免疫刺激。这与“正常”免疫形成对比，后者依赖于共价半抗原-蛋白加合物形成抗原，并主要导致无症状免疫。
