Identifying Cytomegalovirus Complications Using the Quantiferon-CMV Assay After Allogeneic Hematopoietic Stem Cell Transplantation

J Infect Dis. 2017 Jun 1;215(11):1684-1694. doi: 10.1093/infdis/jix192.

Abstract

Background: A simple test to identify recovery of CMV-specific T-cell immunity following hematopoietic stem cell transplantation (HSCT) could assist clinicians in managing CMV-related complications.

Methods: In an observational, multicenter, prospective study of 94 HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9, and 12 months after transplant using the Quantiferon-CMV, an enzyme-linked immunosorbent spot assay (ELISpot), and intracellular cytokine staining.

Results: At 3 months after HSCT, participants who developed CMV disease (n = 8) compared with CMV reactivation (n = 26) or spontaneous viral control (n = 25) had significantly lower CD8+ T-cell production of interferon-γ (IFN-γ) in response to CMV antigens measured by Quantiferon-CMV (P = .0008). An indeterminate Quantiferon-CMV result had a positive predictive value of 83% and a negative predictive value of 98% for identifying participants at risk of further CMV reactivation. Participants experiencing CMV reactivation compared with patients without CMV reactivation had a reduced proportion of polyfunctional (IFN-γ+/tumor necrosis factor α-positive) CD4+ and CD8+ T cells and a higher proportion of interleukin 2-secreting cells (P = .01 and P = .002, respectively).

Conclusions: Quantifying CMV-specific T-cell immunity after HSCT can identify participants at increased risk of clinically relevant CMV-related outcomes.

Keywords: T-cell immunity; cytomegalovirus; immunocompromised host; stem cell transplantation; viral immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / immunology*
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunocompromised Host / immunology
  • Interferon-gamma / analysis
  • Interferon-gamma / metabolism
  • Interferon-gamma Release Tests / methods*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Tumor Necrosis Factor-alpha
  • Interferon-gamma