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. 2010 Jan;84(1):475-81.
doi: 10.1128/JVI.01285-09.

Effect of killer immunoglobulin-like receptors in the response to combined treatment in patients with chronic hepatitis C virus infection

J R Vidal-Castiñeira  1 , A López-Vázquez, R Díaz-Peña, R Alonso-Arias, J Martínez-Borra, R Pérez, J Fernández-Suárez, S Melón, J Prieto, L Rodrigo, C López-Larrea
Affiliations

Effect of killer immunoglobulin-like receptors in the response to combined treatment in patients with chronic hepatitis C virus infection

J R Vidal-Castiñeira et al. J Virol. 2010 Jan.

Abstract

Killer immunoglobulin-like receptors (KIRs) are related to the activation and inhibition of NK cells and may play an important role in the innate response against infection with viruses such as hepatitis C virus (HCV). We examined whether the different combinations of KIRs with their HLA class I ligands influenced the response to combined treatment (pegylated alpha interferon and ribavirin) of patients infected by HCV. A total of 186 consecutive patients diagnosed with chronic HCV infection were analyzed. Seventy-seven patients exhibited HCV RNA levels at 6 months posttreatment and were called nonresponders (NR), while 109 cleared viral RNA and were named sustained viral responders (SVR). Patients were typed for HLA-B, HLA-Cw, KIR genes, and HCV genotype. In our study, the frequency of the KIR2DL2 allele was significantly increased in NR (P < 0.001; odds ratio [OR] = 1.95), as was the frequency of the KIR2DL2/KIR2DL2 genotype (P < 0.005; OR = 2.52). In contrast, the frequencies of the KIR2DL3 genotype (P < 0.001) and KIR2DL3/KIR2DL3 genotype (P < 0.05; OR = 0.54) were significantly increased in the SVR. Different combinations of KIR2DL2 and KIR2DL3 alleles with their ligands were analyzed. The frequency of the KIR2DL2/KIR2DL2-HLA-C1C2 genotype was significantly increased in the NR (P < 0.01; OR = 3.15). Additionally, we found a higher frequency of the KIR2DL3/KIR2DL3-HLA-C1C1 genotype in the SVR group (P < 0.05; OR = 0.33). These results were not affected by the HCV genotype. In conclusion, patients who carried the KIR2DL2/KIR2DL2-HLA-C1C2 genotype were less prone to respond to treatment. However, the KIR2DL3/KIR2DL3-HLA-C1C1 genotype clearly correlated with a satisfactory response to treatment, defined by the clearance of HCV RNA.

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Figures

FIG. 1.
FIG. 1.
KIR allele frequencies for patients with chronic HCV compared to treatment outcome (for KIR2DL2, the P value was <0.001, the OR was 1.95, and the 95% CI was 1.26 to 3.03; for KIR2DL3, the P value was <0.001).
FIG. 2.
FIG. 2.
Percentage of complete response (CR) to combined treatment before the follow-up period. Note that for patients with HCV genotypes 2 and 3, there were 24 weeks of treatment. For patients with HCV genotypes 1 and 4, there were 48 weeks of treatment.
See this image and copyright information in PMC

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