Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment.

OBJECTIVE: Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. METHODS: We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptides (mean of six measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T cells were calculated at baseline and day 15. RESULTS: Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8+ T-cell count <1.0 cells/µL had greater risk of CMV events (adjusted hazard ratio (aHR) 2.84; p 0.054). When the CMI assessment was performed in the immediate post-transplant period (day 15), the presence of <2.0 CD8+ T cells/µL (aHR 2.18; p 0.034) or <1.0 CD4+ T cells/µL (aHR 2.43; p 0.016) also predicted the subsequent development of a CMV event. In addition, lower counts of CMV-specific CD4+ (but not CD8+) T cells at days 60 and 180 were associated with a higher incidence of late-onset events. CONCLUSIONS: Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.

Factors related to the development of CMV-specific CD8+ T cell response in CMV-seropositive solid organ transplant candidates.

This cross-sectional study analyzes factors associated with the development of CMV-specific CD8+ response, measured by IFNg production after cytomegalovirus (CMV) peptide stimulation, in CMV-seropositive solid organ transplantation candidates. A total of 114 candidates were enrolled, of whom 22.8% (26/114) were nonreactive (IFNγ < 0.2 IU/mL). Multivariate logistic regression analysis showed that age, HLA alleles and organ to be transplanted were associated with developing CMV-specific CD8+ immunity (reactive; IFNγ ≥ 0.2 IU/mL). The probability of being reactive was higher in candidates over 50 than in those under 50 (OR 6.33, 95%CI 1.93-20.74). Candidates with HLA-A1 and/or HLA-A2 alleles had a higher probability of being reactive than those with non-HLA-A1/non-HLA-A2 alleles (OR 10.97, 95%CI 3.36-35.83). Renal candidates had a higher probability of being reactive than lung (adjusted OR 8.85, 95%CI 2.24-34.92) and liver candidates (OR 4.87, 95%CI 1.12-21.19). The AUC of this model was 0.84 (p < 0.001). Positive and negative predictive values were 84.8% and 76.9%, respectively. In renal candidates longer dialysis was associated with an increased frequency of reactive individuals (p = 0.040). Therefore, although the assessment of CMV-specific CD8+ response is recommended in all R+ candidates, it is essential in those with a lower probability of being reactive, such as non-renal candidates, candidates under 50 or those with non-HLA-A1/non-HLA-A2 alleles.