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

Abstract

Background and Aims: The role of natural killer (NK) cells in the defense against hepatitis C virus (HCV) infection involve both innate and adaptive immunity. NK cells express a large panel of inhibitory and activating receptors who bind human leukocyte antigen (HLA) class I receptors. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic of these receptors being encoded by genes distributed differently in unrelated individuals. The aim of this study was to look at the immune response in chronic HCV patients by assessing NK-KIR genes and their corresponding HLA ligands.
 Methods: We genotyped 127 chronically HCV-infected patients and 130 non-infected healthy individuals for both KIR genes and their HLA ligands. The HLA-A, HLA-B, HLA-C genotypes were analyzed using polymerase chain reaction high-resolution typing.
 Results: KIR2DL3, KIR2DL5, KIR2DS4 norm, KIR3DL3, KIR2DP1, KIR3DP1 genes were significantly increased in the HCV group compared to healthy individual. Analysis of various HLA haplotypes revealed different HLA alleles associated with increased susceptibility to HCV infection. Thus, HLA A*23:01 was more frequent in the patients’ group than in the controls (p=0.030). At the same time HLA B*44:02 and C*04:02 were significantly elevated in HCV-positive patients (p=0.008 and respectively p= 0.007).
 Conclusions: These results suggest that the expression of KIR2DL3, KIR2DL5, KIR2DS4 norm, KIR3DL3 genes and the association with HLA alleles such as HLA A*23:01, B*44:02, C*04:02 may increase the patient susceptibility to chronic HCV infection.

Increased Prevalence of Unstable HLA-C Variants in HIV-1 Rapid-Progressor Patients

“…HLA-C has been widely studied for its pivotal role in the immune cellular response to viral infections. Previously published studies linked specific HLA-C variants to HPV-related cervical disease [ 27 ] to patients chronically infected by HCV [ 28 ] and by HBV [ 29 ]. The focus of this work was to determine whether there was an association between HLA-C variants’ stability and HIV-1 infection control.…”

Antiviral prophylaxis, male gender and killer immunoglobulin-like receptor KIR2DL3 as markers for stratifying the risk of BK polyomavirus-associated nephropathy in kidney transplant recipients

“…The authors suggested that KIR2DL3 in combination with HLA-C1 or C1C1 contributes to failure of the spontaneous clearance of HCV when the effect of IL28B is considered [23]. This observation was confirmed by others [24,25]. Several studies also linked KIR2DL3 with the spontaneous resolution of HCV infection [26].…”

Current HLA Investigations on SARS-CoV-2 and Perspectives

“…Additional HLA typing and statistical inference of HLA alleles can refine the SNP association signals to specific HLA alleles, reflecting specific molecular functions and pathways. Such a strategy was successfully implemented for infectious diseases such as HIV, HPV, Dengue, and Ebola ( Lin et al, 2003 ; Wang et al, 2011 ; Nishida et al, 2016 ; Adebamowo and Adeyemo, 2019 ; Chen et al, 2019 ; Ekenberg et al, 2019 ; Butler-Laporte et al, 2020 ; Chaisri et al, 2020 ; Huang et al, 2020 ; Ursu et al, 2020 ; Yengo et al, 2020 ).…”