CMV-specific T-cell immunity in solid organ transplant recipients at low risk of CMV infection. Chronology and applicability in preemptive therapy

J Infect. 2017 Oct;75(4):336-345. doi: 10.1016/j.jinf.2017.05.020. Epub 2017 Jun 13.

Abstract

Objectives: To characterize whether the CMV-specific cellular immune response can be used as a predictor of the control of CMV infection and disease and determine thresholds in solid organ transplant (SOT) recipients seropositive for CMV (R+).

Methods: The CMV-specific T-cell response was characterized using intracellular cytokine staining and the evolution of clinical and virological parameters were recorded during the first year after transplantation.

Results: Besides having positive CMV serology, only 28.4% patients had positive immunity (CD8+CD69+IFN-γ+ ≥0.25%) at 2 weeks after transplantation. These patients had less indication of preemptive treatment (p = 0.025) and developed less high grade (≥2000 IU/ml) CMV replication episodes (p = 0.006) than patients with no immunity. Of the 49 patients with a pretransplant sample, only 22.4% had positive immunity, and had a detectable immune response early after transplantation (median of 3.7 weeks). However, only 50% of patients with negative pretransplant immunity acquired a positive immune response and it was significantly later, at a median of 11 weeks (p < 0.001). Patients that developed CMV disease had no CMV-specific immunity.

Conclusions: Having CMV-specific CD8+IFN-γ+ cells ≥0.25% before transplant; 0.15% at two weeks or 0.25% at four weeks after transplantation, identifies patients that may spontaneously control CMV infection and may require less monitoring.

Keywords: CMV-specific T-cell immune response; Cytomegalovirus; Immune monitoring; Preemptive therapy; Solid organ transplant patients.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Female
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Monitoring, Immunologic
  • Prospective Studies
  • Risk Factors
  • Time Factors
  • Transplant Recipients*
  • Viral Load

Substances

  • Antiviral Agents
  • Interferon-gamma