CMV-Specific T Cell Monitoring Offers Superior Risk Stratification of CMV-Seronegative Kidney Transplant Recipients of a CMV-Seropositive Donor

Transplantation. 2017 Oct;101(10):e315-e325. doi: 10.1097/TP.0000000000001825.

Abstract

Background: Detectable cytomegalovirus (CMV)-specific T cells in CMV-seronegative kidney transplant recipients (KTRs) have been attributed to an absence of circulating antibodies despite CMV sensitization. The diagnostic value of CMV-specific T cells, however, needs to be implemented in risk stratification for CMV replication.

Methods: Three hundred twenty-six KTRs were studied and classified with respect to CMV serostatus and presence of CMV-specific T cells. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation. CMV-specific T cells directed to CMV-IE1 and CMV-pp65 were measured by interferon-γ Elispot assay.

Results: Nineteen (28%) of 67 D+R- KTRs showed pretransplant CMV-specific T cells. Although no differences were observed for CMV replication, KTRs with CMV-specific T cells presented with lower initial and peak CMV loads (P < 0.05). KTRs with decreasing/undetectable CMV-IE1-specific T cells pretransplantation and posttransplantation were at greatest risk of CMV replication. KTRs with stable/increasing CMV-IE1-specific T cells from pretransplantation to posttransplantation, however, showed low risk of CMV replication (P < 0.001). One hundred sixty-two (80%) of 203 R+ KTRs showed pretransplant CMV-specific T cells. Decreasing/undetectable CMV-IE1-specific T cells from pretransplantation and posttransplantation identified those R+ KTRs at increased risk of CMV replication (65/80 KTRs; 81%; P < 0.001).

Conclusions: Despite CMV prophylaxis, D+R- KTRs are at greatest risk of CMV disease. Our data suggest that monitoring CMV-specific T cell kinetics from pretransplantation to posttransplantation, particularly directed to CMV-IE1, offers superior risk stratification compared with CMV serostatus alone.

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Antibodies, Viral / blood*
  • Antiviral Agents / administration & dosage
  • Biomarkers / blood
  • Cytomegalovirus / drug effects
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / mortality
  • Enzyme-Linked Immunospot Assay
  • Female
  • Humans
  • Interferon-gamma Release Tests
  • Kaplan-Meier Estimate
  • Kidney Transplantation* / adverse effects
  • Kidney Transplantation* / mortality
  • Male
  • Middle Aged
  • Monitoring, Immunologic
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Serologic Tests
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Time Factors
  • Tissue Donors*
  • Treatment Outcome
  • Viral Load
  • Virus Replication
  • Young Adult

Substances

  • Antibodies, Viral
  • Antiviral Agents
  • Biomarkers