Assessing the risk of CMV reactivation and reconstitution of antiviral immune response post bone marrow transplantation by the QuantiFERON-CMV-assay and real time PCR

J Clin Virol. 2018 Feb-Mar:99-100:61-66. doi: 10.1016/j.jcv.2018.01.002. Epub 2018 Jan 9.

Abstract

Background: CMV reactivation is a major cause of severe complications in allogeneic hematopoietic stem cell transplant (HSCT) recipients. The risk of CMV reactivation depends on the serostatus (+/-) of the donor (D) and recipient (R). The reconstitution of CMV-specific T-cell responses after transplantation is crucial for the control of CMV reactivation.

Objectives: The study aimed to determine the cellular immune status correlating with protection from high-level CMV viremia (>5000 copies/ml) and disease.

Study design: We monitored CMV-specific cellular immune responses in 9 high-risk (D-/R+), 14 intermediate risk (D+/R+) and 3 low risk individuals (D+/R-), and 8 CMV negative controls (D-/R-). Interferon- γ (IFN-γ) levels as a marker for the CD8+ T-cell response were determined by the QuantiFERON-CMV-assay and compared to viral loads determined by PCR.

Results: Early CMV reactivation was detected in all high-risk and 13/14 intermediate risk individuals. High-level viremia was detected in 5/7 high and 7/14 intermediate risk patients. Reconstitution of the CMV-specific cellular immune response started from 3 months after transplantation and resulted in protection against CMV reactivation. Re-establishing of CMV-specific T-cell immune responses with IFN- γ levels >8.9 IU/ml is crucial for protection from high-level CMV viremia.

Conclusions: Monitoring of HSCT-recipients with the QuantiFERON-CMV-assay might be of great benefit to optimize antiviral treatment.

Keywords: Bone marrow transplantation; CD8+ T-cell immunity; CMV reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / immunology
  • DNA, Viral / blood
  • Female
  • Germany
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunity, Cellular
  • Immunoassay* / standards
  • Interferon-gamma / blood
  • Male
  • Middle Aged
  • Postoperative Complications
  • Real-Time Polymerase Chain Reaction* / standards
  • Tissue Donors
  • Transplant Recipients
  • Viral Load
  • Viremia / diagnosis*
  • Viremia / immunology
  • Virus Activation / immunology*
  • Young Adult

Substances

  • DNA, Viral
  • IFNG protein, human
  • Interferon-gamma