The Clinical Features of Patients with Chronic Hepatitis C Virus Infections Are Associated with Killer Cell Immunoglobulin-Like Receptor Genes and Their Expression on the Surface of Natural Killer Cells

Abstract

Killer cell immunoglobulin-like receptor (KIR) genes are known to play a role in the acute phase of hepatitis C virus (HCV) infection. The present study investigated their roles in chronic HCV (CHCV) infection by analyzing the phenotypes and function of natural killer (NK) and T cells that express KIRs. T cells from CHCV patients showed a more differentiated phenotype, and NK cells exhibited an activated profile. These observations are consistent with the increased expression of the degranulation marker CD107a observed after PMA stimulation. We explored the correlations between the expression of KIR genes and lectin type-C receptors with clinical factors that predict progression to fibrosis and cirrhosis. The expression levels of KIR2DS3 and the functional alleles of KIR2DS4-FL were increased in patients with intermediate and high viral loads. Homozygous KIR2DS4 was also associated with the presence of cirrhosis. In the group of individuals with a shorter infection time who developed cirrhosis, we detected decreased expression of KIR3DL1 in CD56dim NK cells in the presence of its ligand. Similarly, in the group of patients with late CHCV infections complicated with cirrhosis, we detected lower expression of the strong inhibitory receptor NKG2A in CD56bright NK cells. We also detected an increase in NKG2C expression in CD56dim NK cells in CHCV patients who displayed high necroinflammatory activity. Decreased KIR3DL2 expression in CD56dim and CD56bright NK cells was associated with a high body mass index, and KIR3DL2 expression may be one factor associated with the more rapid progression of CHCV to fibrosis in patients.

Liver cirrhosis in HIV/HCV‐coinfected individuals is related to NK cell dysfunction and exhaustion, but not to an impaired NK cell modulation by CD4+ T‐cells

“…It is evident that experimental settings, for example, cytokine prestimulation of NK cells, evaluation of spontaneous degranulation, and interaction with other immune cells are critical when analysing ex vivo NK cell cytotoxicity. Together, our results are consistent with those reporting impaired functionality of NK cells during HCV monoinfection , and also HIV/HCV coinfection . However, they could be also interpreted in the context of a functional NK cell dichotomy, where NK cells display a decreased production of antiviral cytokines but an enhanced basal cytotoxicity, which is impaired when these cells are exposed to their targets .…”

Spectrum and Frequency of Nk Cell Receptor Genes Among Cystic Fibrosis Patients

“…As CF is accompanied by severe infectious lesions of the upper respiratory tract, the treatment of which is far from always effective, it cannot be ruled out, that the genetically induced weakness of the activating receptor site of natural killer cells is affecting this process. It should be noted, that we did not meet such studies in the literature, but based on literary data, which relate mainly to HIV infection [23][24][25] and hepatitis C [26][27][28][29][30], it can be concluded, that the more gentle progression of the disease correlates with increased activation of the functional activity of NK cells.…”

HLA Alleles and KIR Genes in Romanian Patients with Chronic Hepatitis C

“…KIR and HLA alleles were associated with response to antiviral treatment. HLA B*44, DRB*02, DRB*07 were associated with a higher response rate in peginterferon alpha associated with ribavirin treatment [40] and KIR2DS3 has been reported to be associated with the failure to respond to HCV treatment [41].…”