Genotype-associated differential NKG2D expression on CD56+CD3+ lymphocytes predicts response to pegylated-interferon/ribavirin therapy in chronic hepatitis C

Hakusyo Cho, Hirotoshi Ebinuma, Nobuhiro Nakamoto, Kazuo Sugiyama, Shingo Usui, Yuko Wakayama, Nobuhito Taniki, Akihiro Yamaguchi, Shunsuke Shiba, Yoshiyuki Yamagishi, Takaji Wakita, Toshifumi Hibi, Hidetsugu Saito, Takanori Kanai

Research output: Contribution to journalArticle

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Abstract

Hepatitis C virus (HCV) genotype 1 infections are significantly more difficult to eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon. Pretreatment NKG2D expression on peripheral CD56+CD3+ lymphocytes and CD56+CD3-NK cells from cases of chronic hepatitis C were analyzed and assessed by treatment effect. Two strains of HCV were used to co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+ lymphocytes, but not NK cells, was significantly impaired in genotype 1 infection, compared to genotype 2. When peripheral blood mononuclear cells from healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+ lymphocytes, but not NK cells, was observed. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression-correlated IFN-γ production. In conclusion, Decreased NKG2D expression on CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior treatment response to PEG-IFN/ribavirin therapy compared to genotype 2.

Original languageEnglish
Article numbere0125664
JournalPLoS One
Volume10
Issue number5
DOIs
Publication statusPublished - 2015 May 12

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chronic hepatitis C
Lymphocytes
Ribavirin
Chronic Hepatitis C
interferons
Interferons
Viruses
lymphocytes
Genotype
Hepatitis C virus
therapeutics
genotype
Hepacivirus
natural killer cells
Natural Killer Cells
Polyethylene glycols
Therapeutics
pretreatment
Infection
infection

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Genotype-associated differential NKG2D expression on CD56+CD3+ lymphocytes predicts response to pegylated-interferon/ribavirin therapy in chronic hepatitis C. / Cho, Hakusyo; Ebinuma, Hirotoshi; Nakamoto, Nobuhiro; Sugiyama, Kazuo; Usui, Shingo; Wakayama, Yuko; Taniki, Nobuhito; Yamaguchi, Akihiro; Shiba, Shunsuke; Yamagishi, Yoshiyuki; Wakita, Takaji; Hibi, Toshifumi; Saito, Hidetsugu; Kanai, Takanori.

In: PLoS One, Vol. 10, No. 5, e0125664, 12.05.2015.

Research output: Contribution to journalArticle

Cho, Hakusyo ; Ebinuma, Hirotoshi ; Nakamoto, Nobuhiro ; Sugiyama, Kazuo ; Usui, Shingo ; Wakayama, Yuko ; Taniki, Nobuhito ; Yamaguchi, Akihiro ; Shiba, Shunsuke ; Yamagishi, Yoshiyuki ; Wakita, Takaji ; Hibi, Toshifumi ; Saito, Hidetsugu ; Kanai, Takanori. / Genotype-associated differential NKG2D expression on CD56+CD3+ lymphocytes predicts response to pegylated-interferon/ribavirin therapy in chronic hepatitis C. In: PLoS One. 2015 ; Vol. 10, No. 5.
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AU - Nakamoto, Nobuhiro

AU - Sugiyama, Kazuo

AU - Usui, Shingo

AU - Wakayama, Yuko

AU - Taniki, Nobuhito

AU - Yamaguchi, Akihiro

AU - Shiba, Shunsuke

AU - Yamagishi, Yoshiyuki

AU - Wakita, Takaji

AU - Hibi, Toshifumi

AU - Saito, Hidetsugu

AU - Kanai, Takanori

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N2 - Hepatitis C virus (HCV) genotype 1 infections are significantly more difficult to eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon. Pretreatment NKG2D expression on peripheral CD56+CD3+ lymphocytes and CD56+CD3-NK cells from cases of chronic hepatitis C were analyzed and assessed by treatment effect. Two strains of HCV were used to co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+ lymphocytes, but not NK cells, was significantly impaired in genotype 1 infection, compared to genotype 2. When peripheral blood mononuclear cells from healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+ lymphocytes, but not NK cells, was observed. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression-correlated IFN-γ production. In conclusion, Decreased NKG2D expression on CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior treatment response to PEG-IFN/ribavirin therapy compared to genotype 2.

AB - Hepatitis C virus (HCV) genotype 1 infections are significantly more difficult to eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon. Pretreatment NKG2D expression on peripheral CD56+CD3+ lymphocytes and CD56+CD3-NK cells from cases of chronic hepatitis C were analyzed and assessed by treatment effect. Two strains of HCV were used to co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+ lymphocytes, but not NK cells, was significantly impaired in genotype 1 infection, compared to genotype 2. When peripheral blood mononuclear cells from healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+ lymphocytes, but not NK cells, was observed. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression-correlated IFN-γ production. In conclusion, Decreased NKG2D expression on CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior treatment response to PEG-IFN/ribavirin therapy compared to genotype 2.

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