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Title: Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate-Induced Liver Injury in Spanish Patients.
Authors: Stephens, Camilla
Moreno-Casares, Antonia
López-Nevot, Miguel-Ángel
García-Cortés, Miren
Medina-Cáliz, Inmaculada
Hallal, Hacibe
Soriano, German
Roman, Eva
Ruiz-Cabello, Francisco
Romero-Gomez, Manuel
Lucena, M Isabel
Andrade, Raúl J
metadata.dc.contributor.authoraffiliation: [Stephens,C; García-Cortés,M; Medina-Cáliz,I; Lucena,MI; Andrade,RJ] Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, CIBERehd, Málaga, Spain. [Moreno-Casares,A; López-Nevot,MA] Unidad de Gestión Clínica de Laboratorio, Departamento de Bioquímica y Biología Molecular III/Inmunología, Instituto de Investigación Biosanitario de Granada, Complejo Hospitalario de Granada, Universidad de Granada, Granada, Spain. [Hallal,H; Ruiz-Cabello,F] Servicio de Aparato Digestivo, Hospital Morales Meseguer, Murcia, Spain. [Soriano,G; Roman,E] Servicio de Gastroenterología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, CIBERehd, Barcelona, Spain. [Roman,E] Escola Universitària d’Infermeria-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. [Romero-Gomez,M] Unidad de Gestión Clínica de Aparato Digestivo Intercentros, Hospitales Universitarios Virgen Macarena-Virgen del Rocio, CIBERehd, Seville, Spain.
Keywords: Hepatotoxicity;Drug-induced liver injury;Pharmacogenetics;Immune response;HLA;Receptor/ligand;Amoxicilina;Enfermedades autoinmunes;Ácido clavulánico;Enfermedad hepática inducida por drogas;Epítopos;Variación genética;Genotipo;Antígenos HLA;Haplotipos;Humanos;Células asesinas naturales;Ligandos;Subgrupos linfocitarios;Neoplasias;Seudogenes;Receptores KIR
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::Amoxicillin
Medical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Clavulanic Acids::Clavulanic Acid
Medical Subject Headings::Diseases::Substance-Related Disorders::Poisoning::Drug-Induced Liver Injury
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Epitopes
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Killer Cells, Natural
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Ligands
Medical Subject Headings::Anatomy::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets
Medical Subject Headings::Diseases::Neoplasms
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Pseudogenes
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Natural Killer Cell::Receptors, KIR
Issue Date: 26-Aug-2016
Publisher: Frontiers Media
Citation: 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
Abstract: 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.
Description: Journal Article;
metadata.dc.identifier.doi: 10.3389/fphar.2016.00280
ISSN: 1663-9812 (Online)
Appears in Collections:01- Artículos - Complejo Hospitalario Universitario de Granada
01- Artículos - Hospital Virgen de la Victoria
01- Artículos - Hospital Virgen del Rocío
01- Artículos - Hospital Virgen Macarena
01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga
01- Artículos - ibsGRANADA. Instituto de Investigación Biosanitaria de Granada

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