Abstract
Although cytomegalovirus (CMV) specific cell-mediated immunity (CMI) has been suggested as a predictive marker for CMV infection, proper CMI monitoring strategy in CMV-seropositive recipients and optimal method are not defined. The aim of this study was to evaluate two interferon gamma release assays during early post-transplant period as a predictor of the development of CMV infection in CMV-seropositive patients. A total of 124 CMV-seropositive recipients who received kidney transplantation from CMV-seropositive donor were prospectively examined. At pre-transplant and post-transplant 1 and 3 months, CMV-CMIs were tested using QuantiFERON-CMV assay (QF-CMV) and CMV specific T cell ELISPOT against CMV pp65 and IE-1 antigens (pp65-ELISPOT, IE-1-ELISPOT). CMV DNAemia occurred in 16 (12.9%) patients within 3 months after transplant. Post-transplant pp65 or IE-1 ELISPOT response, but not QF-CMV, was significantly associated with CMV DNAemia. The pp65 ELISPOT (cut-off; 30 spots/200,000 cells) and IE-1 ELISPOT (10 spots/200,000 cells) at post-transplant 1 month predicted the risk of post-transplant CMV DNAemia (P = 0.019). Negative predictive values (NPV) for protection from CMV DNAemia in case of positive ELISPOT results were 94.5% (95% CI: 86.9–97.8%) and 97.6% (95% CI: 86.3–99.6%) in pp65-ELISPOT and IE-1-ELISPOT assays, respectively. These results suggest that the variability may exist between CMV ELISPOT assays and QF-CMV, and CMV ELISPOT at post-transplant 1 month can identify the risk of CMV DNAemia in seropositive kidney transplant recipients.
Highlights
Despite advances in management strategies, cytomegalovirus (CMV) infection remains one of the most common and serious complications in kidney transplant recipients [1]
CMV-seropositive recipients are at moderate risk of CMV infection, and universal prophylaxis or preemptive ganciclovir is recommended based on monitoring for CMV DNAemia [2]
The present study evaluated the potential of using QuantiFERON-CMV assay (QF-CMV) and CMV enzyme-linked immunospot (ELISPOT) assays to identify patients at risk of CMV infection in seropositive kidney transplant recipients
Summary
Despite advances in management strategies, cytomegalovirus (CMV) infection remains one of the most common and serious complications in kidney transplant recipients [1]. CMV-seropositive recipients are at moderate risk of CMV infection, and universal prophylaxis or preemptive ganciclovir is recommended based on monitoring for CMV DNAemia [2]. Several reports have suggested that measurement of CMV specific T cell activity might reflect patients’ ability to control the virus and predict the risk for post-transplant viral replication [3,4,5,6,7,8,9,10]. Measurement of IFN-γ release might be a useful immune biomarker for CMV infection. IFN-γ can be measured by enzyme-linked immunospot (ELISPOT) assay to assess T cell immune activity by measuring IFN-γ production following stimulation with CMV antigens such as phosphoprotein 65 (pp65) or immediate early 1 (IE-1)
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