Diagnostic Usefulness of Cytomegalovirus (CMV)-Specific T Cell Immunity in Predicting CMV Infection after Kidney Transplantation: A Pilot Proof-of-Concept Study.

Abstract

BackgroundCytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Currently sero-positivity for CMV IgG before solid organ transplantation is the laboratory test of choice for stratifying the risk of CMV reactivation after solid organ transplantation. Theoretically, CMV-specific cell-mediated immune responses before solid organ transplantation should further categorize patients as high or low risk of CMV development. We therefore evaluated the usefulness of the CMV-specific enzyme-linked immunospot (ELISPOT) assay in kidney transplant (KT) candidates for predicting the development of CMV infections after transplantation.Materials and MethodsAll adult CMV IgG (+) recipients admitted to the KT institute between March 2014 and June 2014 were enrolled, and CMV infections after KT were observed between March 2014 and December 2014. All patients underwent CMV pp65 and IE1-specific ELISPOT assays before transplantation. CMV infection was defined in the presence of CMV antigenemia, CMV syndrome, or tissue-invasive CMV disease. We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves.ResultsA total of 69 transplant recipients involving 54 (78%) living-donor KT, 9 (13%) deceased-donor KT, 3 (4%) kidney-pancreas transplants, and 3 (4%) pancreas transplants were enrolled. Of the 69 patients, 27 (39%) developed CMV infections. There was no association between the IE1-specific ELISPOT assay and CMV infection. However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04).ConclusionNegative pp65-specific ELISPOT assay results before transplantation appear to predict the subsequent development of CMV infections after transplantation in CMV IgG (+) KT recipients. Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.