ABSTRACT
Natural killer (NK) cells play pivotal roles in immune responses against infection with viruses, such as hepatitis C virus (HCV), and killer cell immunoglobulin-like receptors (KIRs) are related to the activation and inhibition of NK cells. The aim of this study was to investigate the possibility that KIR genes and their human leukocyte antigen (HLA) ligands influence progression to cirrhosis in patients infected with genotype 1 of HCV. A total of 145 Brazilian patients with confirmed chronic hepatitis C grouped from F0 to F4 according to fibrosis progression to cirrhosis were evaluated. Genotyping of KIR and HLA genes was performed by polymerase chain reaction with sequence-specific oligonucleotide probes. The HLA-C2 KIR ligand was more frequent in patients than in healthy controls (74.5% vs 64.3%, p = 0.04, odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.03-2.52). Moreover, the HLA-C1C2 genotype was more frequent in patients with advanced fibrosis or cirrhosis (F3-F4 group) than in patients in the F0-F2 group (61.6% vs 44.7%, p = 0.06) and in the F4 group compared with the F0-F3 group (65.7% vs 46.7%, p = 0.05, OR = 2.19, 95% CI = 1.01-4.73). NK and KIR ligands may contribute to the development of liver damage in patients chronically infected by HCV.
Subject(s)
HLA-C Antigens/metabolism , Hepacivirus/immunology , Hepatitis C, Chronic/immunology , Killer Cells, Natural/metabolism , Receptors, KIR/genetics , Adult , Brazil , Disease Progression , Female , Fibrosis , Gene Frequency , Genetic Association Studies , Genotype , HLA-C Antigens/genetics , HLA-C Antigens/immunology , Hepacivirus/pathogenicity , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/physiopathology , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Killer Cells, Natural/virology , Ligands , Liver/immunology , Liver/pathology , Lymphocyte Activation/genetics , Male , Middle Aged , Polymorphism, Genetic , Receptors, KIR/agonistsABSTRACT
The present study demonstrated that patients who have recurrent spontaneous abortions (RSA) presented a decreased number of killer immunoglobulin-like inhibitory receptors (KIR), in particular KIR2DL2. The KIR AA genotype was found increased in comparison with controls. Individuals AA will also be homozygous for 2DL3, which in contrast to 2DL2, show a weaker interaction with C1 ligands and therefore a weaker inhibition. The present study might support that in RSA patients, the balance between inhibitory and activating receptors present in natural killer cells is inclined toward an activating state that may contribute to pregnancy loss.