激活性和抑制性杀伤细胞免疫球蛋白样受体与肿瘤治疗中肝毒性的关系。
The relation between activator and inhibitor killer-cell immunoglobulin-like receptors and hepatotoxicity in oncological treatment.
机构信息
Unit of Pediatric Surgery, Section of Pediatric Oncology, Maternity Hospital Virgen de las Nieves, Granada, Spain.
Section of Pediatrics, Rafael Méndez Hospital, Lorca, Spain.
出版信息
Minerva Pediatr (Torino). 2023 Oct;75(5):668-673. doi: 10.23736/S0026-4946.19.05544-0. Epub 2019 Jun 28.
BACKGROUND
The molecular interactions between killer-cell immunoglobulin-like receptors (KIRs) and their related HLA class I ligands play a central role in regulating the responses of natural killer (NK) cells. Our study aim was to determine the role played by KIR genes and their HLA ligands in the genetic predisposition for the development of hepatotoxicity in children treated with chemotherapy for an oncological process.
METHODS
The study group was composed of 22 children with cancer, being treated with chemotherapy at the Unit of Pediatric Oncology of the Maternity Hospital Virgen de las Nieves (Granada, Spain) and presenting signs of drug-induced liver injury (DILI). Twenty-four children receiving similar treatment but presenting no signs of DILI were selected as a control group.
RESULTS
The children with the KIR K2DS2 were four times more likely to have hepatotoxicity (OR=4.08, P=0.034, 95% CI: 1.1-15). The patients with 2DS2 and the C1 ligand were ten times more likely to undergo an episode of hepatotoxicity (P=0.007).
CONCLUSIONS
KIRs may be risk factors for susceptibility to hepatotoxicity following chemotherapy.
背景
杀伤细胞免疫球蛋白样受体（KIR）与其相关 HLA Ⅰ类配体之间的分子相互作用在调节自然杀伤（NK）细胞反应中起着核心作用。我们的研究目的是确定 KIR 基因及其 HLA 配体在接受化疗治疗肿瘤过程的儿童中发生肝毒性的遗传易感性中的作用。
方法
研究组由 22 名患有癌症的儿童组成，他们在西班牙格拉纳达的圣母妇产医院儿科肿瘤病房接受化疗，并出现药物性肝损伤（DILI）的迹象。选择 24 名接受类似治疗但没有出现 DILI 迹象的儿童作为对照组。
结果
具有 KIR K2DS2 的儿童发生肝毒性的可能性增加了四倍（OR=4.08，P=0.034，95%CI：1.1-15）。具有 2DS2 和 C1 配体的患者发生肝毒性的可能性增加了十倍（P=0.007）。
结论
KIR 可能是化疗后发生肝毒性的易感因素。
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