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.
Hepatitis C virus (HCV)‐infected individuals may have a faster progression of liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) development when influenced by host, viral and environmental factors. Hepatitis C virus disease progression is also associated with genetic variants of specific killer cell immunoglobulin‐like receptors (KIRs) and genes of the major histocompatibility complex (MHC). The aim of the present study was to correlate clinical, virologic and biochemical parameters and to evaluate the possible influence of KIR genes and their HLA class I ligands in patients infected with hepatitis C virus. The present study analysed a total of 127 chronic HCV‐infected patients for various biochemical and genetics factors that can influence disease progression and prognosis. Liver function parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), direct bilirubin (DB), alpha‐fetoprotein (AFP), HCV RNA levels and fibrosis indices were analysed using well‐established biochemical methods. At the same time, KIR and HLA genotyping was performed using a polymerase chain reaction sequence‐specific primer technique. Analysis of HLA class I and HLA ligands revealed that HLA‐C*12:02 and HLA‐A3 and HLA‐A11 were positively associated with the F3‐F4 fibrosis group (p = .026; OR = 8.717, CI = 1.040–73.077; respectively, p = .047; OR = 2.187; 95% CI = 1.066–4.486). KIR2DL2‐positive patients had high median levels of AST after treatment and direct bilirubin levels when compared to KIR2DL2‐negative patients (p = .013, respectively, p = .028). KIR2DL2/KIR2DL2‐C1C1 genotype was associated with increased AST, ALT and GGT levels. A higher GGT level was also observed in KIR2DS2‐C1‐positive patients when compared to KIR2DS2‐C1‐negative patients. The present research demonstrates several links between specific clinical, virologic and biochemical parameters and the expression of KIR genes and their HLA ligands in HCV‐infected patients. These connections should be taken into account when considering disease development and treatment.
Background:The presence of anti-HLA antibodies, especially the presence of donor specific antibodies was associated with graft rejection after transplantation. The aim of our work was to analyze whether there is a correlation between actual-crossmatch performed by Luminex and virtual-crossmatch assessed on the basis of recipient's anti-HLA antibody specificities.Material and Methods: Anti-HLA antibodies screening ± identification and crossmatch tests were performed before renal transplantation in 310 potential recipients, using Luminex technology. For all patients and donors, pretransplant HLA genotyping for A, B, and DRB1 loci were performed using molecular biology methods. To perform virtual crossmatch, the recipient's HLA-antibody specificities were compared against the donor HLA alleles. Results:The anti-HLA antibodies screening was positive in 65 recipients (103 positive results): 15 patients (23%) presented anti-HLA class I antibodies, 12 patients (18.5%) had anti-HLA class II antibodies and in 38 subjects (58.5%) we discovered both types of antibodies. Using LSA assay, we could determine the antibody specificities only in 87 cases. Comparing the recipient's anti-HLA antibody specificities with donor's HLA antigens we found positive virtual-crossmatch in 81 cases. For 620 crossmatch results, the sensitivity, specificity, positive and negative predictive values were 87.6%, 97.8%, 85.5% and 98.1%, respectively. Conclusion:virtual-crossmatch assessed on the basis of recipient's anti-HLA antibody specificities had a good correlation with actual-crossmatch performed by Luminex and thus, had a high sensitivity in predicting donor-recipient immunologic compatibility. Using the virtual crossmatch may improve graft allocation strategy for kidney recipients reducing the waiting time on the waiting list.
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