BackgroundUncontrolled cytomegalovirus (CMV) replication in immunocompromised solid-organ transplant recipients is a clinically relevant issue and an indication of impaired CMV-specific cell-mediated immunity (CMI). Primary aim of this study was to assess the suitability of the immune monitoring tool T-Track® CMV to determine CMV-reactive CMI in a cohort of hemodialysis patients representative of patients eligible for renal transplantation. Positive and negative agreement of T-Track® CMV with CMV serology was examined in 124 hemodialysis patients, of whom 67 (54%) revealed a positive CMV serostatus. Secondary aim of the study was to evaluate T-Track® CMV performance against two unrelated CMV-specific CMI monitoring assays, QuantiFERON®-CMV and a cocktail of six class I iTAg™ MHC Tetramers.ResultsPositive T-Track® CMV results were obtained in 90% (60/67) of CMV-seropositive hemodialysis patients. In comparison, 73% (45/62) and 77% (40/52) positive agreement with CMV serology was achieved using QuantiFERON®-CMV and iTAg™ MHC Tetramer. Positive T-Track® CMV responses in CMV-seropositive patients were dominated by pp65-reactive cells (58/67 [87%]), while IE-1-responsive cells contributed to an improved (87% to 90%) positive agreement of T-Track® CMV with CMV serology. Interestingly, T-Track® CMV, QuantiFERON®-CMV and iTAg™ MHC Tetramers showed 79% (45/57), 87% (48/55) and 93% (42/45) negative agreement with serology, respectively, and a strong inter-assay variability. Notably, T-Track® CMV was able to detect IE-1-reactive cells in blood samples of patients with a negative CMV serology, suggesting either a previous exposure to CMV that yielded a cellular but no humoral immune response, or TCR cross-reactivity with foreign antigens, both suggesting a possible protective immunity against CMV in these patients.ConclusionT-Track® CMV is a highly sensitive assay, enabling the functional assessment of CMV-responsive cells in hemodialysis patients prior to renal transplantation. T-Track® CMV thus represents a valuable immune monitoring tool to identify candidate transplant recipients potentially at increased risk for CMV-related clinical complications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-017-0194-z) contains supplementary material, which is available to authorized users.
Background Impairment of Cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) by immunosuppressive therapy is a major cause for uncontrolled CMV replication and related clinical complications. Objective The aim of the study was to assess the suitability of the immune monitoring tool T-Track® CMV to determine CMV-reactive CMI in hemodialysis patients. Study Design Positive and negative agreement of T-Track® CMV with CMV-serology have been examined in a cohort of 124 hemodialysis patients of whom 67 (54%) revealed a positive CMV serostatus and compared with that of QuantiFERON®-CMV and a mixture of 6 CMV iTAG tetramers. Results Positive T-Track® CMV, QuantiFERON®-CMV and CMV tetramer results were obtained in 60/67, 45/62 and 40/52 CMV-seropositive hemodialysis patients resulting in 89.6%, 72.6% and 76.9% positive agreement with CMV-serology, respectively. Positive T-Track® CMV responses were dominated by pp65-reactive cells (58/67 (86.6%)), whereas IE-1 responsive cells were observed in 33/67 (49.3%) CMV-seropositive patients. T-Track® CMV, QuantiFERON®-CMV and CMV tetramers showed 78.9% (45/57), 87.3% (48/55) and 93.3% (42/45) negative agreement with serology respectively. Notably, T-Track® CMV-positive tests in seronegative patients were mostly caused by IE1-reactive cells at low spot counts. Conclusion T-Track® CMV represents a sensitive assay format, enabling functional assessment of the network of clinically relevant subpopulations of CMV-responsive cells. Thus, T-Track® CMV may represent a valuable tool to identify patients at increased risk for CMV-related clinical complications and may help to guide personalized antiviral and immunosuppressive therapy.
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