Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection

Systemic chronic active Epstein-Barr virus infection (sCAEBV) is an intractable disease that present activated EBV-infected T- or NK-cells and their clonal proliferation. When inflammatory symptoms persist and proceed, a lethal complication of hemophagocytic lymphohistiocytosis (HLH) develops, but i...

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Main Authors: Yu Uemura, Ayaka Ohashi, Mayumi Yoshimori, Miwako Nishio, Tsuneaki Hirakawa, Norio Shimizu, Naomi Wada, Ken-Ichi Imadome, Ayako Arai
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Virology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fviro.2022.999929/full
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author Yu Uemura
Ayaka Ohashi
Ayaka Ohashi
Ayaka Ohashi
Mayumi Yoshimori
Mayumi Yoshimori
Miwako Nishio
Tsuneaki Hirakawa
Norio Shimizu
Naomi Wada
Ken-Ichi Imadome
Ayako Arai
Ayako Arai
Ayako Arai
author_facet Yu Uemura
Ayaka Ohashi
Ayaka Ohashi
Ayaka Ohashi
Mayumi Yoshimori
Mayumi Yoshimori
Miwako Nishio
Tsuneaki Hirakawa
Norio Shimizu
Naomi Wada
Ken-Ichi Imadome
Ayako Arai
Ayako Arai
Ayako Arai
author_sort Yu Uemura
collection DOAJ
description Systemic chronic active Epstein-Barr virus infection (sCAEBV) is an intractable disease that present activated EBV-infected T- or NK-cells and their clonal proliferation. When inflammatory symptoms persist and proceed, a lethal complication of hemophagocytic lymphohistiocytosis (HLH) develops, but its biomarker to represent the pathophysiology and an effective agent to cure have not been developed as of today. It is known that interferon-γ (IFN-γ) level in the peripheral blood increases in HLH correlatedly with the disease condition and that antagonistic anti-IFN-γ antibody is effective against HLH. We examined the plasma level of IFN-γ to investigate its role in the disease condition of sCAEBV. sCAEBV was diagnosed based on the criteria conforming to the definition of sCAEBV in the WHO classification issued in 2017. As it was previously reported, disease activity was defined as the condition positive for any one of the followings: fever, liver dysfunction, progressive skin lesions, vasculitis, and uveitis. Eighteen sCAEBV patients were examined. Their plasma IFN-γ levels were significantly higher than those of healthy donors. The levels in sCAEBV patients with disease activity were higher than those without disease activity. The mRNA expression of IFNG was detected in EBV-infected cells of all patients. We also detected a correlation between plasma IFN-γ levels and mRNA levels of EBV-infected cells in peripheral blood mononuclear cells. These results suggest that EBV-infected cells produce IFN-γ in sCAEBV. Although the difference was not significant, the patients whose plasma IFN-γ levels at diagnosis were higher than 40 pg/mL tended to result in poorer survival than those with lower levels. We concluded that plasma IFN-γ is a potential biomarker that indicates disease activity of sCAEBV. Further study shall confirm its significance.
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spelling doaj.art-acce7c86f39e4b6291b9311a283404e12022-12-22T03:22:02ZengFrontiers Media S.A.Frontiers in Virology2673-818X2022-09-01210.3389/fviro.2022.999929999929Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infectionYu Uemura0Ayaka Ohashi1Ayaka Ohashi2Ayaka Ohashi3Mayumi Yoshimori4Mayumi Yoshimori5Miwako Nishio6Tsuneaki Hirakawa7Norio Shimizu8Naomi Wada9Ken-Ichi Imadome10Ayako Arai11Ayako Arai12Ayako Arai13Division of Hematology and Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, JapanDivision of Hematology and Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, JapanDepartment of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, JapanDepartment of Laboratory Molecular Genetics of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Laboratory Molecular Genetics of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Hematological Therapeutics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Laboratory Molecular Genetics of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDivision of Hematology and Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, JapanCenter of Stem Cell and Regenerative Medicine, Advanced Multidisciplinary Research Cluster, Institute of Research, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Advanced Medicine for Viral Infections, National Center for Child Health and Development, Tokyo, JapanDepartment of Advanced Medicine for Viral Infections, National Center for Child Health and Development, Tokyo, JapanDivision of Hematology and Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, JapanDepartment of Laboratory Molecular Genetics of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Hematological Therapeutics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanSystemic chronic active Epstein-Barr virus infection (sCAEBV) is an intractable disease that present activated EBV-infected T- or NK-cells and their clonal proliferation. When inflammatory symptoms persist and proceed, a lethal complication of hemophagocytic lymphohistiocytosis (HLH) develops, but its biomarker to represent the pathophysiology and an effective agent to cure have not been developed as of today. It is known that interferon-γ (IFN-γ) level in the peripheral blood increases in HLH correlatedly with the disease condition and that antagonistic anti-IFN-γ antibody is effective against HLH. We examined the plasma level of IFN-γ to investigate its role in the disease condition of sCAEBV. sCAEBV was diagnosed based on the criteria conforming to the definition of sCAEBV in the WHO classification issued in 2017. As it was previously reported, disease activity was defined as the condition positive for any one of the followings: fever, liver dysfunction, progressive skin lesions, vasculitis, and uveitis. Eighteen sCAEBV patients were examined. Their plasma IFN-γ levels were significantly higher than those of healthy donors. The levels in sCAEBV patients with disease activity were higher than those without disease activity. The mRNA expression of IFNG was detected in EBV-infected cells of all patients. We also detected a correlation between plasma IFN-γ levels and mRNA levels of EBV-infected cells in peripheral blood mononuclear cells. These results suggest that EBV-infected cells produce IFN-γ in sCAEBV. Although the difference was not significant, the patients whose plasma IFN-γ levels at diagnosis were higher than 40 pg/mL tended to result in poorer survival than those with lower levels. We concluded that plasma IFN-γ is a potential biomarker that indicates disease activity of sCAEBV. Further study shall confirm its significance.https://www.frontiersin.org/articles/10.3389/fviro.2022.999929/fullsystemic chronic active Epstein-Barr virus infection (sCAEBV)Epstein- Barr virusT cellNK cellinterferon-γhemophagocytic lymphohistiocytosis (HLH)
spellingShingle Yu Uemura
Ayaka Ohashi
Ayaka Ohashi
Ayaka Ohashi
Mayumi Yoshimori
Mayumi Yoshimori
Miwako Nishio
Tsuneaki Hirakawa
Norio Shimizu
Naomi Wada
Ken-Ichi Imadome
Ayako Arai
Ayako Arai
Ayako Arai
Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection
Frontiers in Virology
systemic chronic active Epstein-Barr virus infection (sCAEBV)
Epstein- Barr virus
T cell
NK cell
interferon-γ
hemophagocytic lymphohistiocytosis (HLH)
title Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection
title_full Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection
title_fullStr Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection
title_full_unstemmed Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection
title_short Plasma interferon-γ concentration: a potential biomarker of disease activity of systemic chronic active Epstein-Barr virus infection
title_sort plasma interferon γ concentration a potential biomarker of disease activity of systemic chronic active epstein barr virus infection
topic systemic chronic active Epstein-Barr virus infection (sCAEBV)
Epstein- Barr virus
T cell
NK cell
interferon-γ
hemophagocytic lymphohistiocytosis (HLH)
url https://www.frontiersin.org/articles/10.3389/fviro.2022.999929/full
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