Goh Shawn J R, Tuomisto Johanna E E, Purcell Anthony W, Mifsud Nicole A, Illing Patricia T
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic., Australia.
Allergy. 2021 Jan;76(1):150-167. doi: 10.1111/all.14355. Epub 2020 Jul 6.
Penicillin refers to a group of beta-lactam antibiotics that are the first-line treatment for a range of infections. However, they also possess the ability to form novel antigens, or neoantigens, through haptenation of proteins and can stimulate a range of immune-mediated adverse reactions-collectively known as drug hypersensitivity reactions (DHRs). IgE-mediated reactions towards these neoantigens are well studied; however, IgE-independent reactions are less well understood. These reactions usually manifest in a delayed manner as different forms of cutaneous eruptions or liver injury consistent with priming of an immune response. Ex vivo studies have confirmed the infiltration of T cells into the site of inflammation, and the subsets of T cells involved appear dependent on the nature of the reaction. Here, we review the evidence that has led to our current understanding of these immune-mediated reactions, discussing the nature of the lesional T cells, the characterization of drug-responsive T cells isolated from patient blood, and the potential mechanisms by which penicillins enter the antigen processing and presentation pathway to stimulate these deleterious responses. Thus, we highlight the need for a more comprehensive understanding of the underlying genetic and molecular basis of penicillin-induced DHRs.
青霉素是一类β-内酰胺抗生素，是一系列感染的一线治疗药物。然而，它们也具有通过蛋白质半抗原化形成新抗原的能力，并能引发一系列免疫介导的不良反应，统称为药物超敏反应（DHRs）。针对这些新抗原的IgE介导反应已得到充分研究；然而，IgE非依赖性反应的了解较少。这些反应通常以延迟的方式表现为不同形式的皮肤疹或与免疫反应启动一致的肝损伤。体外研究证实T细胞浸润到炎症部位，且所涉及的T细胞亚群似乎取决于反应的性质。在此，我们回顾了使我们对这些免疫介导反应有当前认识的证据，讨论了病变T细胞的性质、从患者血液中分离出的药物反应性T细胞的特征，以及青霉素进入抗原加工和呈递途径以刺激这些有害反应的潜在机制。因此，我们强调需要更全面地了解青霉素诱导的DHRs的潜在遗传和分子基础。
