RT Journal Article
T1 Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate-Induced Liver Injury in Spanish Patients.
A1 Stephens, Camilla
A1 Moreno-Casares, Antonia
A1 López-Nevot, Miguel-Ángel
A1 García-Cortés, Miren
A1 Medina-Cáliz, Inmaculada
A1 Hallal, Hacibe
A1 Soriano, German
A1 Roman, Eva
A1 Ruiz-Cabello, Francisco
A1 Romero-Gomez, Manuel
A1 Lucena, M Isabel
A1 Andrade, Raúl J
K1 Hepatotoxicity
K1 Drug-induced liver injury
K1 Pharmacogenetics
K1 Immune response
K1 HLA
K1 Receptor/ligand
K1 Amoxicilina
K1 Enfermedades autoinmunes
K1 Ácido clavulánico
K1 Enfermedad hepática inducida por drogas
K1 Epítopos
K1 Variación genética
K1 Genotipo
K1 Antígenos HLA
K1 Haplotipos
K1 Humanos
K1 Células asesinas naturales
K1 Ligandos
K1 Subgrupos linfocitarios
K1 Neoplasias
K1 Seudogenes
K1 Receptores KIR
AB Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown. In this study, we examined KIR gene profiles and HLA class I polymorphisms in amoxicillin-clavulanate (AC) DILI patients in search for potential risk associations. One hundred and two AC DILI patients and 226 controls were genotyped for the presence or absence of 16 KIR loci, including the two pseudogenes 2DP1 and 3DP1. No significant differences were found in the distribution of individual KIRs between patients and controls, which were comparable to previously reported KIR data from ethnically similar cohorts. The 21.6 and 21.2% of the patients and controls, respectively, were homozygous haplotype A carriers, while 78.4 and 78.8%, respectively, contained at least one B haplotype (Bx). The genotypes translated into 27 (AC DILI) and 46 (controls) different gene profiles, with 19 being present in both groups. The most frequent Bx gene profile containing KIRs 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2, 3DL3, 2DL4, and 3PD1 was present in 16% of the DILI patients and 14% of the controls. The distribution of HLA class I epitopes did not differ significantly between AC DILI patients and controls. The most frequent receptor-ligand combinations in the DILI patients were 2DL3 + epitope C1 (67%) and 3DL1 + Bw4 motif (67%), while 2DL1 + epitope C2 (69%) and 3DL1 + Bw4 motif (69%) predominated in the controls. This is to our knowledge the first analysis of KIR receptor-HLA ligand associations in DILI, although our findings do not support evidence of these genetic variations playing a major role in AC DILI development.
PB Frontiers Media
YR 2016
FD 2016-08-26
LK http://hdl.handle.net/10668/2563
UL http://hdl.handle.net/10668/2563
LA en
NO Stephens C, Moreno-Casares A, López-Nevot MÁ, García-Cortés M, Medina-Cáliz I, Hallal H, et al. Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate-Induced Liver Injury in Spanish Patients. Front Pharmacol. 2016; 7:280
NO Journal Article;
DS RISalud
RD Apr 19, 2025