Journal Article

Validation of T-Track® CMV to assess the functionality of cytomegalovirus-reactive cell-mediated immunity in hemodialysis patients

Böger, Carsten A., Lückhoff, Gerhard, Schemmerer, Mathias, Köstler, Josef, Bendfeldt, Hanna, Krämer, Bernhard K., Wagner, Ralf, Banas, Bernhard, Deml, Ludwig, Barabas, Sascha, Batzilla, Julia, Leicht, Joachim, Krüger, Bernd, Rascle, Anne

2017

Overview

Background Uncontrolled 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. Results Positive 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. Conclusion T-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.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Adult / Aged / Aged, 80 and over / Allergology / Antibodies, Viral - blood / Antigens / Biomedical and Life Sciences / Biomedicine / Cell division / Cell-mediated immunity / Cells, Cultured / Chicken pox / Cohort Studies / Cross-reactivity / Cytokines and Growth Factors / Cytomegalovirus / Cytomegalovirus - immunology / Cytomegalovirus Infections - diagnosis / Cytomegalovirus Infections - immunology / Female / Flow cytometry / Hemodialysis / Herpes viruses / Humans / Immediate-Early Proteins - immunology / Immune response (humoral) / Immunity to infection / Immunity, Cellular / Immunoassay / Immunocompromised Host / Immunology / Infections / Kidney Failure, Chronic - diagnosis / Kidney Failure, Chronic - immunology / Kidney Failure, Chronic - therapy / Kidney Transplantation / Lymphocytes / Major histocompatibility complex / Male / Middle Aged / Monitoring, Immunologic - methods / Observer Variation / Patients / Peptides / Phosphoproteins - immunology / Pp65 protein / Proteins / Renal Dialysis / Research Article / Sensitivity and Specificity / Serology / Software / T cell receptors / Transplants & implants / Vaccine / Viral infections / Viral Matrix Proteins - immunology / Waiting Lists