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KIR, HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan

Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR) in combination with its cognate human leukocyte antigen (HLA) ligand, especially KIR2DL3-HLA-C1, is associated with both treatment-induced and spon...

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Autores principales: Nozawa, Yuichi, Umemura, Takeji, Joshita, Satoru, Katsuyama, Yoshihiko, Shibata, Soichiro, Kimura, Takefumi, Morita, Susumu, Komatsu, Michiharu, Matsumoto, Akihiro, Tanaka, Eiji, Ota, Masao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861489/
https://www.ncbi.nlm.nih.gov/pubmed/24349500
http://dx.doi.org/10.1371/journal.pone.0083381
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author Nozawa, Yuichi
Umemura, Takeji
Joshita, Satoru
Katsuyama, Yoshihiko
Shibata, Soichiro
Kimura, Takefumi
Morita, Susumu
Komatsu, Michiharu
Matsumoto, Akihiro
Tanaka, Eiji
Ota, Masao
author_facet Nozawa, Yuichi
Umemura, Takeji
Joshita, Satoru
Katsuyama, Yoshihiko
Shibata, Soichiro
Kimura, Takefumi
Morita, Susumu
Komatsu, Michiharu
Matsumoto, Akihiro
Tanaka, Eiji
Ota, Masao
author_sort Nozawa, Yuichi
collection PubMed
description Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR) in combination with its cognate human leukocyte antigen (HLA) ligand, especially KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection in Caucasians, these innate immunity genes have not been fully clarified in Japanese patients. We therefore investigated 16 KIR genotypes along with HLA-B and -C ligands and a genetic variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1 patients who underwent pegylated-interferon-α2b (PEG-IFN) and ribavirin therapy. HLA-Bw4 was significantly associated with a sustained virological response (SVR) to treatment (P = 0.017; odds ratio [OR] = 2.50, ), as was the centromeric A/A haplotype of KIR (P = 0.015; OR 3.37). In contrast, SVR rates were significantly decreased in patients with KIR2DL2 or KIR2DS2 (P = 0.015; OR = 0.30, and P = 0.025; OR = 0.32, respectively). Multivariate logistic regression analysis subsequently identified the IL28B TT genotype (P = 0.00009; OR = 6.87, 95% confidence interval [CI] = 2.62 - 18.01), KIR2DL2/HLA-C1 (P = 0.014; OR = 0.24, 95% CI = 0.08 - 0.75), KIR3DL1/HLA-Bw4 (P = 0.008, OR = 3.32, 95% CI = 1.37 - 8.05), and white blood cell count at baseline (P = 0.009; OR = 3.32, 95% CI = 1.35 - 8.16) as independent predictive factors of an SVR. We observed a significant association between the combination of IL28B TT genotype and KIR3DL1-HLA-Bw4 in responders (P = 0.0019), whereas IL28B TT along with KIR2DL2-HLA-C1 was related to a non-response (P = 0.0067). In conclusion, combinations of KIR3DL1/HLA-Bw4, KIR2DL2/HLA-C1, and a genetic variant of the IL28B gene are predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients infected with genotype 1b HCV.
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spelling pubmed-38614892013-12-17 KIR, HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan Nozawa, Yuichi Umemura, Takeji Joshita, Satoru Katsuyama, Yoshihiko Shibata, Soichiro Kimura, Takefumi Morita, Susumu Komatsu, Michiharu Matsumoto, Akihiro Tanaka, Eiji Ota, Masao PLoS One Research Article Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR) in combination with its cognate human leukocyte antigen (HLA) ligand, especially KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection in Caucasians, these innate immunity genes have not been fully clarified in Japanese patients. We therefore investigated 16 KIR genotypes along with HLA-B and -C ligands and a genetic variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1 patients who underwent pegylated-interferon-α2b (PEG-IFN) and ribavirin therapy. HLA-Bw4 was significantly associated with a sustained virological response (SVR) to treatment (P = 0.017; odds ratio [OR] = 2.50, ), as was the centromeric A/A haplotype of KIR (P = 0.015; OR 3.37). In contrast, SVR rates were significantly decreased in patients with KIR2DL2 or KIR2DS2 (P = 0.015; OR = 0.30, and P = 0.025; OR = 0.32, respectively). Multivariate logistic regression analysis subsequently identified the IL28B TT genotype (P = 0.00009; OR = 6.87, 95% confidence interval [CI] = 2.62 - 18.01), KIR2DL2/HLA-C1 (P = 0.014; OR = 0.24, 95% CI = 0.08 - 0.75), KIR3DL1/HLA-Bw4 (P = 0.008, OR = 3.32, 95% CI = 1.37 - 8.05), and white blood cell count at baseline (P = 0.009; OR = 3.32, 95% CI = 1.35 - 8.16) as independent predictive factors of an SVR. We observed a significant association between the combination of IL28B TT genotype and KIR3DL1-HLA-Bw4 in responders (P = 0.0019), whereas IL28B TT along with KIR2DL2-HLA-C1 was related to a non-response (P = 0.0067). In conclusion, combinations of KIR3DL1/HLA-Bw4, KIR2DL2/HLA-C1, and a genetic variant of the IL28B gene are predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients infected with genotype 1b HCV. Public Library of Science 2013-12-12 /pmc/articles/PMC3861489/ /pubmed/24349500 http://dx.doi.org/10.1371/journal.pone.0083381 Text en © 2013 Nozawa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nozawa, Yuichi
Umemura, Takeji
Joshita, Satoru
Katsuyama, Yoshihiko
Shibata, Soichiro
Kimura, Takefumi
Morita, Susumu
Komatsu, Michiharu
Matsumoto, Akihiro
Tanaka, Eiji
Ota, Masao
KIR, HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan
title KIR, HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan
title_full KIR, HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan
title_fullStr KIR, HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan
title_full_unstemmed KIR, HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan
title_short KIR, HLA, and IL28B Variant Predict Response to Antiviral Therapy in Genotype 1 Chronic Hepatitis C Patients in Japan
title_sort kir, hla, and il28b variant predict response to antiviral therapy in genotype 1 chronic hepatitis c patients in japan
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861489/
https://www.ncbi.nlm.nih.gov/pubmed/24349500
http://dx.doi.org/10.1371/journal.pone.0083381
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