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

J Infect Dis. 2019 Aug 9;220(6):1001-1007. doi: 10.1093/infdis/jiz237.

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: CD134; T cells; allogeneic hematopoietic stem cell transplantation; digital polymerase chain reaction; human herpesvirus 6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • CD4-Positive T-Lymphocytes
  • DNA, Viral
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Herpesvirus 6, Human / genetics*
  • Herpesvirus 6, Human / metabolism*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Polymerase Chain Reaction / methods*
  • Prospective Studies
  • Receptors, OX40 / immunology*
  • Roseolovirus Infections / immunology*
  • Roseolovirus Infections / virology
  • Viral Load
  • Young Adult

Substances

  • DNA, Viral
  • Receptors, OX40
  • TNFRSF4 protein, human