Human Herpesvirus 6 Reactivation Evaluated by Digital Polymerase Chain Reaction and Its Association With Dynamics of CD134-Positive T Cells After Allogeneic Hematopoietic Stem Cell Transplantation

Hitomi Nakayama, Rie Yamazaki, Jun Kato, Yuya Koda, Masatoshi Sakurai, Ryohei Abe, Shintaro Watanuki, Chieko Sumiya, Kohei Shiroshita, Shinya Fujita, Kentaro Yamaguchi, Shinichiro Okamoto, Takehiko Mori

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Human herpesvirus 6 (HHV-6) causes life-threatening central nervous system disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent studies implicated CD134 as a specific receptor of HHV-6B and demonstrated that its expression levels in CD4-positive T cells after allo-HSCT could be related to the reactivation of HHV-6. We prospectively evaluated the relationship between HHV-6 reactivation and CD134+ T cells in the recipients of allo-HSCT. METHODS: HHV-6 viral load in plasma was quantitatively measured weekly after allo-HSCT by digital polymerase chain reaction in 34 patients. The ratio of CD134 in CD4+ T cells (CD134/CD4 ratio) was serially measured by flow cytometry before and after transplantation. RESULTS: HHV-6 reactivation was detected in 23 patients (68%). The CD134/CD4 ratio before conditioning was significantly higher in patients with HHV-6 reactivation than in those without (median, 3.8% vs 1.5%, P < .01). In multivariate analysis, a higher CD134/CD4 ratio before conditioning was significantly associated with the incidence of HHV-6 reactivation (odds ratio, 10.5 [95% confidence interval, 1.3-85.1], P = .03). CONCLUSIONS: A higher CD134/CD4 ratio before conditioning was associated with a higher risk of HHV-6 reactivation, suggesting that the rate may be a promising marker for predicting HHV-6 reactivation after allo-HSCT.

Original languageEnglish
Pages (from-to)1001-1007
Number of pages7
JournalThe Journal of infectious diseases
Volume220
Issue number6
DOIs
Publication statusPublished - 2019 Aug 9

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Human Herpesvirus 6
Hematopoietic Stem Cell Transplantation
T-Lymphocytes
Polymerase Chain Reaction
Central Nervous System Diseases
Viral Load
Flow Cytometry
Multivariate Analysis
Transplantation
Odds Ratio
Confidence Intervals

Keywords

  • allogeneic hematopoietic stem cell transplantation
  • CD134
  • digital polymerase chain reaction
  • human herpesvirus 6
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

@article{ab06ecc84168400ba9c94eb0de8df1ed,
title = "Human Herpesvirus 6 Reactivation Evaluated by Digital Polymerase Chain Reaction and Its Association With Dynamics of CD134-Positive T Cells After Allogeneic Hematopoietic Stem Cell Transplantation",
abstract = "BACKGROUND: Human herpesvirus 6 (HHV-6) causes life-threatening central nervous system disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent studies implicated CD134 as a specific receptor of HHV-6B and demonstrated that its expression levels in CD4-positive T cells after allo-HSCT could be related to the reactivation of HHV-6. We prospectively evaluated the relationship between HHV-6 reactivation and CD134+ T cells in the recipients of allo-HSCT. METHODS: HHV-6 viral load in plasma was quantitatively measured weekly after allo-HSCT by digital polymerase chain reaction in 34 patients. The ratio of CD134 in CD4+ T cells (CD134/CD4 ratio) was serially measured by flow cytometry before and after transplantation. RESULTS: HHV-6 reactivation was detected in 23 patients (68{\%}). The CD134/CD4 ratio before conditioning was significantly higher in patients with HHV-6 reactivation than in those without (median, 3.8{\%} vs 1.5{\%}, P < .01). In multivariate analysis, a higher CD134/CD4 ratio before conditioning was significantly associated with the incidence of HHV-6 reactivation (odds ratio, 10.5 [95{\%} confidence interval, 1.3-85.1], P = .03). CONCLUSIONS: A higher CD134/CD4 ratio before conditioning was associated with a higher risk of HHV-6 reactivation, suggesting that the rate may be a promising marker for predicting HHV-6 reactivation after allo-HSCT.",
keywords = "allogeneic hematopoietic stem cell transplantation, CD134, digital polymerase chain reaction, human herpesvirus 6, T cells",
author = "Hitomi Nakayama and Rie Yamazaki and Jun Kato and Yuya Koda and Masatoshi Sakurai and Ryohei Abe and Shintaro Watanuki and Chieko Sumiya and Kohei Shiroshita and Shinya Fujita and Kentaro Yamaguchi and Shinichiro Okamoto and Takehiko Mori",
year = "2019",
month = "8",
day = "9",
doi = "10.1093/infdis/jiz237",
language = "English",
volume = "220",
pages = "1001--1007",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "6",

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TY - JOUR

T1 - Human Herpesvirus 6 Reactivation Evaluated by Digital Polymerase Chain Reaction and Its Association With Dynamics of CD134-Positive T Cells After Allogeneic Hematopoietic Stem Cell Transplantation

AU - Nakayama, Hitomi

AU - Yamazaki, Rie

AU - Kato, Jun

AU - Koda, Yuya

AU - Sakurai, Masatoshi

AU - Abe, Ryohei

AU - Watanuki, Shintaro

AU - Sumiya, Chieko

AU - Shiroshita, Kohei

AU - Fujita, Shinya

AU - Yamaguchi, Kentaro

AU - Okamoto, Shinichiro

AU - Mori, Takehiko

PY - 2019/8/9

Y1 - 2019/8/9

N2 - BACKGROUND: Human herpesvirus 6 (HHV-6) causes life-threatening central nervous system disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent studies implicated CD134 as a specific receptor of HHV-6B and demonstrated that its expression levels in CD4-positive T cells after allo-HSCT could be related to the reactivation of HHV-6. We prospectively evaluated the relationship between HHV-6 reactivation and CD134+ T cells in the recipients of allo-HSCT. METHODS: HHV-6 viral load in plasma was quantitatively measured weekly after allo-HSCT by digital polymerase chain reaction in 34 patients. The ratio of CD134 in CD4+ T cells (CD134/CD4 ratio) was serially measured by flow cytometry before and after transplantation. RESULTS: HHV-6 reactivation was detected in 23 patients (68%). The CD134/CD4 ratio before conditioning was significantly higher in patients with HHV-6 reactivation than in those without (median, 3.8% vs 1.5%, P < .01). In multivariate analysis, a higher CD134/CD4 ratio before conditioning was significantly associated with the incidence of HHV-6 reactivation (odds ratio, 10.5 [95% confidence interval, 1.3-85.1], P = .03). CONCLUSIONS: A higher CD134/CD4 ratio before conditioning was associated with a higher risk of HHV-6 reactivation, suggesting that the rate may be a promising marker for predicting HHV-6 reactivation after allo-HSCT.

AB - BACKGROUND: Human herpesvirus 6 (HHV-6) causes life-threatening central nervous system disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent studies implicated CD134 as a specific receptor of HHV-6B and demonstrated that its expression levels in CD4-positive T cells after allo-HSCT could be related to the reactivation of HHV-6. We prospectively evaluated the relationship between HHV-6 reactivation and CD134+ T cells in the recipients of allo-HSCT. METHODS: HHV-6 viral load in plasma was quantitatively measured weekly after allo-HSCT by digital polymerase chain reaction in 34 patients. The ratio of CD134 in CD4+ T cells (CD134/CD4 ratio) was serially measured by flow cytometry before and after transplantation. RESULTS: HHV-6 reactivation was detected in 23 patients (68%). The CD134/CD4 ratio before conditioning was significantly higher in patients with HHV-6 reactivation than in those without (median, 3.8% vs 1.5%, P < .01). In multivariate analysis, a higher CD134/CD4 ratio before conditioning was significantly associated with the incidence of HHV-6 reactivation (odds ratio, 10.5 [95% confidence interval, 1.3-85.1], P = .03). CONCLUSIONS: A higher CD134/CD4 ratio before conditioning was associated with a higher risk of HHV-6 reactivation, suggesting that the rate may be a promising marker for predicting HHV-6 reactivation after allo-HSCT.

KW - allogeneic hematopoietic stem cell transplantation

KW - CD134

KW - digital polymerase chain reaction

KW - human herpesvirus 6

KW - T cells

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U2 - 10.1093/infdis/jiz237

DO - 10.1093/infdis/jiz237

M3 - Article

C2 - 31063196

AN - SCOPUS:85071345557

VL - 220

SP - 1001

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JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

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