Background: Current pre-transplant risk stratification for Cytomegalovirus (CMV) infection is based on donor/recipient (D/R) IgG-serostatus and clinical variables such as the use of T-cell depletion induction therapy and rescue therapies after acute rejection (AR). However, CMV-specific T-cell immunity (CTI) controls viral replication and its assessment may add information to guide decision-making regarding preventive strategies.

Methods: 315 consecutive kidney transplant patients were analyzed to evaluate main baseline clinical and immunological factors associated to CMV infection (CMV replication) and disease (tissue invasive). Also, we added pre-transplant CTI against two dominant CMV antigens (IE-1 and pp656) using the IFN-γ ELISPOT assay.

Results: 63/315(20%) patients displayed infection and 34/315(10.8%) were diagnosed of CMV disease. 109/315(34.6%) received rATG induction, 125/315(39.7%) received prophylaxis, 37/315(11.7%) were D+/R-, 204/315(64.8%) were D+/R+, 74/315(23.5%) were D- and 294/315(93.3%) were treated with CNI drugs.

Out of all clinical and demographic variables, D/R serostatus and use of rATG discriminated CMV infection (OR 1.514, p=0.014 and OR 2.346, p=0.003). Induction with rATG and rescue therapy after AR correlated with CMV disease (OR 3.543 p=0.001 and OR 8.968 p=0.009). Pre-transplant CTI against IE-1 and pp65 were significantly higher in R+ as compared to R- (p<0.001). IE-1 and pp65 CTI strongly correlated (R=0.49 p<0.001). 16/73(21.9%) R- had detectable IE-1 and pp65 CTI frequencies, whereas 47/242(19.4%) R+ did not. Negative CTI to IE-1 and pp65 discriminated patients at risk of CMV infection (OR 2.238 p=0.005 and OR 2.346 p=0.003) and disease (OR 4.424 p=<0.001 and OR 4.088 p<0.001). Interestingly, a double negative CTI for both antigens significantly correlated with CMV infection (OR 2.562 p=0.001) and disease (OR 5.128 p<0.001).

In the multivariate analysis, double negative CTI (OR 2.294 p=0.017) was the only independent predictor of CMV infection. Induction with rATG (OR 4.979 p=0.006), receiving rescue treatment for AR (OR 5.547 p<0.001) and double negative CTI (OR 4.843, p<0.001), independently predicted CMV disease.

Conclusions: Pre-transplant CTI should be added as an additional tool to predict the immune-risk of CMV infection after kidney transplantation.

CITATION INFORMATION: Crespo E, Jarque M, Luque S, Melilli E, Manonelles A, Gil-Vernet S, Cruzado J, Grinyó J, Bestard O. Pre-Transplant CMV-Specific T-Cell Immunity Is an Additional Independent Variable Predicting CMV Infection After Kidney Transplantation. Am J Transplant. 2017;17 (suppl 3).

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