Pretransplant interferon-γ secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation

Abstract

In this prospective study we analyzed pretransplant interferon-γ secretion by cytomegalovirus (CMV)-specific CD8+ T cells to assess its possible utility in determining the risk of CMV replication after solid organ transplantation. A total of 113 lung and kidney transplant patients were enrolled in the study but only 55 were evaluable. All CMV-seronegative recipients were pretransplant "nonreactive" (IFNγ <0.2 IU/mL) (11/11), whereas 30/44 (68.2%) CMV-seropositive (R+) recipients were "reactive" (IFNγ ≥0.2 IU/mL) and 14/44 (31.8%) were "nonreactive". In the R(+) "nonreactive" group, 7/14 (50%) developed posttransplant CMV replication, whereas the virus replicated only in 4/30 (13.3%) of the R(+) "reactive" patients (p = 0.021). According to the best multivariate model, pretransplant "nonreactive" recipients receiving an organ from a CMV-seropositive donor had a 10-fold increased risk of CMV replication compared to pretransplant "reactive" recipients (adjusted OR 10.49, 95% CI 1.88-58.46). This model displayed good discrimination ability (AUC 0.80) and calibration (Hosmer-Lemeshow test, p = 0.92). Negative and positive predictive values were 83.7% and 75%, respectively. The accuracy of the model was 82%. Therefore, assessment of interferon-γ secretion by cytomegalovirus (CMV)-specific CD8+ T cells prior to transplantation is useful in informing the risk of posttransplant CMV replication in solid organ transplant patients. One-third of cytomegalovirus-seropositive solid organ transplant candidates do not have pretransplant detectable interferon-gamma production by cytomegalovirus-specific CD8+ T cells and are at higher risk of posttransplant cytomegalovirus replication, indicating that assessment of pretransplant interferon-gamma production might contribute to a novel design of the antiviral prevention strategy. © 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.