J Korean Med Sci.  2011 Nov;26(11):1483-1488. 10.3346/jkms.2011.26.11.1483.

Frequency of Killer Cell Immunoglobulin-like Receptors (KIRs) in Korean Patients with Chronic HCV Infection

• Sung PS
• Choi HB
• Kim SY
• Hong SW
• Park CH
• Song MJ
• Lee SW
• Yoo CR
• Choi SW
• Han NI
• Kim TG
• Yoon SK

• KMID: 1123449
• DOI: http://doi.org/10.3346/jkms.2011.26.11.1483

Abstract

Natural killer (NK) cells play an important role in innate immunity, especially in the response to viral infections, such as hepatitis C virus (HCV). Killer cell immunoglobulin-like receptors (KIRs) are the primary receptors of NK cells that mediate innate immunity. KIRs are also involved in acquired immunity, because some KIRs are expressed on the surface of certain subsets of T cells. In this study, the frequency of KIR genes, HLA-C allotypes, and combinations of KIR genes with their HLA-C ligands were evaluated in two different groups of the Korean population: controls and patients with chronic HCV infection. The study population consisted of 147 Korean patients with chronic HCV infection. The frequency of KIR2DS2 in patients with chronic HCV infection was 9.5% which was significantly lower than 19.5% of the control (P < 0.01). However, there were no significant differences in the frequency of other KIR genes, HLA-C allotypes or different combinations of KIR genes with their HLA-C ligands. This study can contribute to the further prospective study with a larger scale, suggesting the assumption that KIR2DS2 might aid in HCV clearance by enhancing both the innate and acquired immune responses of people in Korea.

Keyword

Hepatitis C Virus; Chronic Infection; Receptors, KIR; Korea

MeSH Terms

Adult
Aged
Female
Genes, MHC Class I
Genotype
HLA-C Antigens/genetics
Hepacivirus/immunology
Hepatitis C, Chronic/*genetics/immunology
Humans
Killer Cells, Natural/immunology/virology
Male
Middle Aged
Receptors, KIR/*genetics/immunology
Republic of Korea
T-Lymphocyte Subsets/immunology

Reference

1. Bostan N, Mahmood T. An overview about hepatitis C: a devastating virus. Crit Rev Microbiol. 2010. 36:91–133.

2. Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL. Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology. 1999. 29:908–914.

3. Lim YS. Current status of liver disease in Korea: hepatitis C. Korean J Hepatol. 2009. 15:S25–S28.

4. Shin HR. Epidemiology of hepatitis C virus in Korea. Intervirology. 2006. 49:18–22.

5. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005. 5:215–229.

6. Doherty DG, Norris S, Madrigal-Estebas L, McEntee G, Traynor O, Hegarty JE, O'Farrelly C. The human liver contains multiple populations of NK cells, T cells, and CD3+ CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J Immunol. 1999. 163:2314–2321.

7. Liu ZX, Govindarajan S, Okamoto S, Dennert G. NK cells cause liver injury and facilitate the induction of T cell-mediated immunity to a viral liver infection. J Immunol. 2000. 164:6480–6486.

8. Moretta A, Biassoni R, Bottino C, Pende D, Vitale M, Poggi A, Mingari MC, Moretta L. Major histocompatibility complex class I-specific receptors on human natural killer and T lymphocytes. Immunol Rev. 1997. 155:105–117.

9. Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002. 20:217–251.

10. Khakoo SI, Carrington M. KIR and disease: a model system or system of models? Immunol Rev. 2006. 214:186–201.

11. Williams AP, Bateman AR, Khakoo SI. Hanging in the balance. KIR and their role in disease. Mol Interv. 2005. 5:226–240.

12. Vivier E, Anfossi N. Inhibitory NK-cell receptors on T cells: witness of the past, actors of the future. Nat Rev Immunol. 2004. 4:190–198.

13. Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, Tyan D, Lanier LL, Parham P. Human diversity in killer cell inhibitory receptor genes. Immunity. 1997. 7:753–763.

14. Boyton RJ, Altmann DM. Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease. Clin Exp Immunol. 2007. 149:1–8.

15. Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, Cheng J, Goedert JJ, Vlahov D, Hilgartner M, Cox S, Little AM, Alexander GJ, Cramp ME, O'Brien SJ, Rosenberg WM, Thomas DL, Carrington M. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science. 2004. 305:872–874.

16. Norman PJ, Carrington CV, Byng M, Maxwell LD, Curran MD, Stephens HA, Chandanayingyong D, Verity DH, Hameed K, Ramdath DD, Vaughan RW. Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations. Genes Immun. 2002. 3:86–95.

17. Djulejic E, Petlichkovski A, Trajkov D, Hristomanova S, Middleton D, Spiroski M. Distribution of killer cell immunoglobulin-like receptors in the Macedonian population. Hum Immunol. 2010. 71:281–288.

18. Thimme R, Bukh J, Spangenberg HC, Wieland S, Pemberton J, Steiger C, Govindarajan S, Purcell RH, Chisari FV. Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad Sci U S A. 2002. 99:15661–15668.

19. Su AI, Pezacki JP, Wodicka L, Brideau AD, Supekova L, Thimme R, Wieland S, Bukh J, Purcell RH, Schultz PG, Chisari FV. Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci U S A. 2002. 99:15669–15674.

20. Whang DH, Park H, Yoon JA, Park MH. Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families. Hum Immunol. 2005. 66:146–154.

21. Wang SH, Huang CX, Ye L, Wang X, Song L, Wang YJ, Liang H, Huang XY, Ho WZ. Natural killer cells suppress full cycle HCV infection of human hepatocytes. J Viral Hepat. 2008. 15:855–864.

22. van Bergen J, Thompson A, van der Slik A, Ottenhoff TH, Gussekloo J, Koning F. Phenotypic and functional characterization of CD4 T cells expressing killer Ig-like receptors. J Immunol. 2004. 173:6719–6726.

23. Askar M, Avery R, Corey R, Lopez R, Thomas D, Pidwell D, Eghtesad B, Miller C, Fung J, Zein NN. Lack of killer immunoglobulin-like receptor 2DS2 (KIR2DS2) and KIR2DL2 is associated with poor responses to therapy of recurrent hepatitis C virus in liver transplant recipients. Liver Transpl. 2009. 15:1557–1563.

24. Vidal-Castiñeira JR, López-Vázquez A, Díaz-Peña R, Alonso-Arias R, Martínez-Borra J, Pérez R, Fernández-Suárez J, Melón S, Prieto J, Rodrigo L, López-Larrea C. Effect of killer immunoglobulin-like receptors in the response to combined treatment in patients with chronic hepatitis C virus infection. J Virol. 2010. 84:475–481.

25. Knapp S, Warshow U, Hegazy D, Brackenbury L, Guha IN, Fowell A, Little AM, Alexander GJ, Rosenberg WM, Cramp ME, Khakoo SI. Consistent beneficial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to hepatitis C virus. Hepatology. 2010. 51:1168–1175.