title: Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.
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. Pre-treatment 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Po-sung
authors.initials: PS
authors.lastname: Chu
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Ebinuma
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakamoto
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Usui
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Wakayama
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Taniki
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Shiba
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamagishi
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Center for Advanced IBD Research and Treatment, Kitasato Institute Hospital, Kitasato University, Tokyo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan; Division of Pharmacotherapeutics, School of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D017252:CD3 Complex; D019002:CD56 Antigen; D004338:Drug Combinations; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C527085:KLRK1 protein, human