Hepatitis C virus-specific T-cell response correlates with hepatitis activity and donor IL28B genotype early after liver transplantation

Ryuichiro Tsuzaki; Akinobu Takaki; Takahito Yagi; Fusao Ikeda; Kazuko Koike; Yoshiaki Iwasaki; Hidenori Shiraha; Yasuhiro Miyake; Hiroshi Sadamori; Susumu Shinoura; Yuzo Umeda; Ryuichi Yoshida; Daisuke Nobuoka; Masashi Utsumi; Eiichi Nakayama; Toshiyoshi Fujiwara; Kazuhide Yamamoto

Hepatitis C virus-specific T-cell response correlates with hepatitis activity and donor IL28B genotype early after liver transplantation

Ryuichiro Tsuzaki, Akinobu Takaki, Takahito Yagi, Fusao Ikeda, Kazuko Koike, Yoshiaki Iwasaki, Hidenori Shiraha, Yasuhiro Miyake, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Masashi Utsumi, Eiichi Nakayama, Toshiyoshi Fujiwara, Kazuhide Yamamoto

Research output: Contribution to journal › Article › peer-review

Abstract

It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-speciflc immune responses by measuring the peripheral blood mononuclear cell-derived HCV-speciflc interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At > 3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-speciflc immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.

Original language	English
Pages (from-to)	291-302
Number of pages	12
Journal	Acta medica Okayama
Volume	68
Issue number	5
Publication status	Published - 2014

Keywords

CD4 T cell
Dendritic cell
ELISPOT assay
Interferon gamma
Single nucleotide polymorphisms

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Tsuzaki, R., Takaki, A., Yagi, T., Ikeda, F., Koike, K., Iwasaki, Y., Shiraha, H., Miyake, Y., Sadamori, H., Shinoura, S., Umeda, Y., Yoshida, R., Nobuoka, D., Utsumi, M., Nakayama, E., Fujiwara, T., & Yamamoto, K. (2014). Hepatitis C virus-specific T-cell response correlates with hepatitis activity and donor IL28B genotype early after liver transplantation. Acta medica Okayama, 68(5), 291-302.

Tsuzaki, R, Takaki, A, Yagi, T, Ikeda, F, Koike, K, Iwasaki, Y , Shiraha, H, Miyake, Y, Sadamori, H, Shinoura, S, Umeda, Y, Yoshida, R, Nobuoka, D, Utsumi, M, Nakayama, E, Fujiwara, T & Yamamoto, K 2014, 'Hepatitis C virus-specific T-cell response correlates with hepatitis activity and donor IL28B genotype early after liver transplantation', Acta medica Okayama, vol. 68, no. 5, pp. 291-302.

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abstract = "It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-speciflc immune responses by measuring the peripheral blood mononuclear cell-derived HCV-speciflc interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At > 3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-speciflc immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.",

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AU - Tsuzaki, Ryuichiro

AU - Takaki, Akinobu

AU - Yagi, Takahito

AU - Ikeda, Fusao

AU - Koike, Kazuko

AU - Iwasaki, Yoshiaki

AU - Shiraha, Hidenori

AU - Miyake, Yasuhiro

AU - Sadamori, Hiroshi

AU - Shinoura, Susumu

AU - Umeda, Yuzo

AU - Yoshida, Ryuichi

AU - Nobuoka, Daisuke

AU - Utsumi, Masashi

AU - Nakayama, Eiichi

AU - Fujiwara, Toshiyoshi

AU - Yamamoto, Kazuhide

PY - 2014

Y1 - 2014

N2 - It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-speciflc immune responses by measuring the peripheral blood mononuclear cell-derived HCV-speciflc interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At > 3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-speciflc immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.

AB - It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-speciflc immune responses by measuring the peripheral blood mononuclear cell-derived HCV-speciflc interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At > 3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-speciflc immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.

KW - CD4 T cell

KW - Dendritic cell

KW - ELISPOT assay

KW - Interferon gamma

KW - Single nucleotide polymorphisms

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SN - 0386-300X

VL - 68

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JO - Acta medica Okayama

JF - Acta medica Okayama

IS - 5

ER -

Hepatitis C virus-specific T-cell response correlates with hepatitis activity and donor IL28B genotype early after liver transplantation

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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