Preformed frequencies of cytomegalovirus (CMV)-specific memory T and B cells identify protected CMV-sensitized individuals among seronegative kidney transplant recipients

Clin Infect Dis. 2014 Dec 1;59(11):1537-45. doi: 10.1093/cid/ciu589. Epub 2014 Jul 21.


Background: Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers.

Methods: We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG-seronegative (sR(-)) and 86 CMV IgG-seropositive (sR(+)) patients. Clinical outcome was evaluated in both groups.

Results: All sR(+) patients showed a wide range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell frequencies were also clearly detected in 30% of sR(-) patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test.

Conclusions: Assessment of CMV-specific memory T- and B-cell responses before kidney transplantation among sR(-) recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection.

Keywords: CMV infection; T- and B-cell ELISPOT assay; adaptive immunity; kidney transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / immunology*
  • Case-Control Studies
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / prevention & control*
  • Enzyme-Linked Immunospot Assay
  • Female
  • Humans
  • Interferon-gamma / immunology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • ROC Curve
  • Retrospective Studies
  • T-Lymphocytes / immunology*
  • Transplantation Immunology


  • Interferon-gamma