Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders

被引:24
作者
Carneiro, Valdirene Leao [1 ]
Lemaire, Denise C. [1 ,2 ,3 ]
Bendicho, Maria Teresita [1 ,2 ]
Souza, Sabrina L. [4 ,5 ]
Cavalcante, Lourianne Nascimento [4 ,5 ]
Angelo, Ana Luisa [1 ]
Freire, Songeli Menezes [1 ,2 ]
Cardeal Mendes, Carlos Mauricio [6 ]
Santana, Nelma [4 ,5 ]
Costa Lyra, Luiz G. [4 ,5 ]
Lyra, Andre Castro [1 ,4 ,5 ]
机构
[1] Univ Fed Bahia, Hlth Sci Inst, Postgrad Program Immunol, Salvador, BA, Brazil
[2] Bahiana Sch Med & Publ Hlth EBMSP, Salvador, BA, Brazil
[3] State Univ Bahia UNEB, Salvador, BA, Brazil
[4] Univ Fed Bahia, Hosp Univ Prof Edgar Santos C HUPES, Gastro Hepatol Serv, Salvador, BA, Brazil
[5] Hosp Sao Rafael, Salvador, BA, Brazil
[6] Univ Fed Bahia, Fima Lifshitz Res Ctr, Salvador, BA, Brazil
关键词
antiviral therapy; chronic hepatitis C; HLA-C; interferon; KIR; natural killer cells; HEPATOCELLULAR-CARCINOMA; KIR; NK; INTERFERON;
D O I
10.1111/j.1478-3231.2010.02212.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy. Methods We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits. Results We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P < 0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001). Conclusions Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.
引用
收藏
页码:567 / 573
页数:7
相关论文
共 25 条
[1]   Human pathogen subversion of antigen presentation [J].
Brodsky, FM ;
Lem, L ;
Solache, A ;
Bennett, EM .
IMMUNOLOGICAL REVIEWS, 1999, 168 :199-215
[2]  
Dustin LB, 2007, ANNU REV IMMUNOL, V25, P71, DOI 10.1146/annurev.immunol.25.022106.141602
[3]   Human KIR2DL5 is an inhibitory receptor expressed on the surface of NK and T lymphocyte subsets [J].
Estefania, Ernesto ;
Flores, Raquel ;
Gomez-Lozano, Natalia ;
Aguilar, Helena ;
Lopez-Botet, Miguel ;
Vilches, Carlos .
JOURNAL OF IMMUNOLOGY, 2007, 178 (07) :4402-4410
[4]   Estimating progression to cirrhosis in chronic hepatitis C virus infection [J].
Freeman, AJ ;
Dore, GJ ;
Law, MG ;
Thorpe, M ;
Von Overbeck, J ;
Lloyd, AR ;
Marinos, G ;
Kaldor, JM .
HEPATOLOGY, 2001, 34 (04) :809-816
[5]   The killer cell immunoglobulin-like receptor (KIR) genomic region: gene-order, haplotypes and allelic polymorphism [J].
Hsu, KC ;
Chida, S ;
Dupont, B ;
Geraghty, DE .
IMMUNOLOGICAL REVIEWS, 2002, 190 (01) :40-52
[6]   Decrease of CD56+T cells and natural killer cells in cirrhotic livers with hepatitis C may be involved in their susceptibility to hepatocellular carcinoma [J].
Kawarabayashi, N ;
Seki, S ;
Hatsuse, K ;
Ohkawa, T ;
Koike, Y ;
Aihara, T ;
Habu, Y ;
Nakagawa, R ;
Ami, K ;
Hiraide, H ;
Mochizuki, H .
HEPATOLOGY, 2000, 32 (05) :962-969
[7]   KIR and disease: a model system or system of models? [J].
Khakoo, Salim I. ;
Carrington, Mary .
IMMUNOLOGICAL REVIEWS, 2006, 214 :186-201
[8]   HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection [J].
Khakoo, SI ;
Thio, CL ;
Martin, MP ;
Brooks, CR ;
Gao, XJ ;
Astemborski, J ;
Cheng, J ;
Goedert, JJ ;
Vlahov, D ;
Hilgartner, M ;
Cox, S ;
Little, AM ;
Alexander, GJ ;
Cramp, ME ;
O'Brien, SJ ;
Rosenberg, WMC ;
Thomas, DL ;
Carrington, M .
SCIENCE, 2004, 305 (5685) :872-874
[9]   IN SEARCH OF THE MISSING SELF - MHC MOLECULES AND NK CELL RECOGNITION [J].
LJUNGGREN, HG ;
KARRE, K .
IMMUNOLOGY TODAY, 1990, 11 (07) :237-244
[10]   Protective effect of the HLA-Bw4I80 epitope and the killer cell immunoglobulin-like receptor 3DS1 gene against the development of hepatocellular carcinoma in patients with hepatitis C virus infection [J].
López-Vázquez, A ;
Rodrigo, L ;
Martinez-Borra, J ;
Pérez, R ;
Rodríguez, M ;
Fdez-Morera, JL ;
Fuentes, D ;
Rodriguez-Rodero, S ;
González, S ;
López-Larrea, C .
JOURNAL OF INFECTIOUS DISEASES, 2005, 192 (01) :162-165