The relation between activator and inhibitor killer-cell immunoglobulin-like receptors and hepatotoxicity in oncological treatment.

Abstract

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. 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. 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). KIRs may be risk factors for susceptibility to hepatotoxicity following chemotherapy.