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

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.

• Authors: J R Vidal-Castiñeira, 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
• Journal: Journal of virology (J Virol) Vol. 84 Issue 1 Pg. 475-81 (Jan 2010) ISSN: 1098-5514 [Electronic] United States
• PMID: 19846535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• HLA Antigens
• Interferon-alpha
• KIR2DL2 protein, human
• RNA, Viral
• Receptors, KIR
• Receptors, KIR2DL2
• Receptors, KIR2DL3
• Ribavirin

Topics

• Adult
• Antiviral Agents (therapeutic use)
• Drug Therapy, Combination
• Female
• Genotype
• HLA Antigens (genetics)
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy, immunology)
• Humans
• Interferon-alpha (therapeutic use)
• Male
• Middle Aged
• Pharmacogenetics (methods)
• RNA, Viral (blood)
• Receptors, KIR (genetics)
• Receptors, KIR2DL2
• Receptors, KIR2DL3
• Ribavirin (therapeutic use)
• Treatment Outcome
• Viral Load (drug effects)