Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver reactions. Although expression of HLA-B*57:01 increases susceptibility, little is known about the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the presentation of flucloxacillin-modified peptides by the risk allele. In this study, the binding of flucloxacillin to proteins of liver-like cells was characterized. Flucloxacillin was shown to bind to proteins localized in bile canaliculi regions, coinciding with the site of clinical disease. The localization of flucloxacillin was mediated primarily by the membrane transporter multidrug resistance-associated protein 2. Modification of multiple proteins by flucloxacillin in bile canaliculi regions may provide a potential local source of neo-antigens for HLA presentation in the liver.

中文翻译：

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细胞膜转运蛋白促进肝细胞氟氯西林蛋白加合物的积累：对氟氯西林诱导的肝损伤的影响

氟氯西林是一种β-内酰胺类抗生素，与药物引起的肝脏反应发生率高有关。尽管 HLA-B*57:01 的表达增加了易感性，但对诱导临床表型所涉及的病理机制知之甚少。不可逆的蛋白质修饰被怀疑通过风险等位基因呈递氟氯西林修饰的肽来驱动反应。在这项研究中，氟氯西林与肝样细胞蛋白质的结合被表征。氟氯西林被证明与位于胆管区域的蛋白质结合，与临床疾病的部位相吻合。氟氯西林的定位主要由膜转运蛋白多药耐药相关蛋白 2 介导。