Relationship between beta-herpesviruses reactivation and development of complications after autologous peripheral blood stem cell transplantation

J Med Virol. 2012 Dec;84(12):1953-60. doi: 10.1002/jmv.23412.

Abstract

The relationship between beta-herpesviruses reactivation and the development of complications after autologous peripheral blood stem cell transplantation was investigated. Viral genomic sequences were detected by the polymerase chain reaction, virus-specific antibodies by ELISA, and human herpesvirus (HHV)-6 variants by restriction endonuclease analysis. Virus reactivation, serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, soluble IL-2 receptor (sIL-2R), IL-2, and IL-4 were compared with clinical features in 44 patients before and after transplantation. Anti-CMV and anti-HHV-6 antibodies were found in 70.5% and 81.8% of patients, respectively. The frequency of plasma viremia was significantly higher in patients after transplantation (41% vs. 11.4%). Reactivation of more than one virus was identified in 55.6% of patients and reactivation of HHV-7 alone in 44.4%. In cases of concurrent infection, HHV-7 was reactivated before HHV-6, and both HHV-6 and HHV-7 were reactivated before CMV. There was a significant increase in HHV-6 load in peripheral blood leukocytes DNA during viremia. In all cases HHV-6B variant was detected. Complications after transplantation occurred in 27.3% of patients and virus reactivation was detected in all patients with complications. The significant increases in the rate of HHV-6 and HHV-7 reactivation and in serum levels of TNF-α, IL-1β, and sIL-2R, as well as aggravated immunosuppression, suggest that both viruses were involved in the complications after autologous peripheral blood stem cell transplantation, via their immunomodulatory activity. The kinetics of reactivation suggests a potential role of HHV-7 as a co-factor of HHV-6 reactivation, and of both HHV-6 and HHV-7 as co-factors of CMV reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus / pathogenicity*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / virology
  • DNA, Viral / analysis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / virology
  • Herpesvirus 6, Human / pathogenicity*
  • Herpesvirus 6, Human / physiology
  • Herpesvirus 7, Human / pathogenicity*
  • Herpesvirus 7, Human / physiology
  • Humans
  • Interleukin-1beta / blood
  • Interleukin-2 / blood
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation / adverse effects*
  • Postoperative Complications / immunology
  • Postoperative Complications / virology*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Interleukin-2 / blood
  • Retrospective Studies
  • Transplantation, Autologous / adverse effects
  • Tumor Necrosis Factor-alpha / blood
  • Viral Load
  • Viremia / pathology
  • Viremia / virology
  • Virus Activation*
  • Young Adult

Substances

  • Antibodies, Viral
  • DNA, Viral
  • IL2 protein, human
  • Interleukin-1beta
  • Interleukin-2
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha