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

• Published in: BMC immunology Vol. 18; no. 1; p. 15
• Main Authors: Banas, Bernhard, Böger, Carsten A, Lückhoff, Gerhard, Krüger, Bernd, Barabas, Sascha, Batzilla, Julia, Schemmerer, Mathias, Köstler, Josef, Bendfeldt, Hanna, Rascle, Anne, Wagner, Ralf, Deml, Ludwig, Leicht, Joachim, Krämer, Bernhard K
• Format: Journal Article
• Language: English
• Published: England BioMed Central 07-03-2017
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Viral - blood; Antigens; Cell division; Cell-mediated immunity; Cells, Cultured; Chicken pox; Cohort Studies; Cross-reactivity; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus Infections - diagnosis; Cytomegalovirus Infections - immunology; Female; Flow cytometry; Hemodialysis; Herpes viruses; Humans; Immediate-Early Proteins - immunology; Immune response; Immune response (humoral); Immune system; Immunity, Cellular; Immunoassay; Immunocompromised Host; Infections; Kidney Failure, Chronic - diagnosis; Kidney Failure, Chronic - immunology; Kidney Failure, Chronic - therapy; Kidney Transplantation; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Male; Middle Aged; Monitoring, Immunologic - methods; Observer Variation; Patients; Peptides; Phosphoproteins - immunology; Pp65 protein; Proteins; Renal Dialysis; Sensitivity and Specificity; Serology; Software; T cell receptors; Transplants & implants; Viral infections; Viral Matrix Proteins - immunology; Waiting Lists; Germany; Cytomegalovirus; IE-1; Cell-mediated immunity; Hemodialysis; IFN-γ ELISpot; QuantiFERON®-CMV; pp65; CMV; T-Track® CMV; iTAg™ MHC Tetramers
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/s12865-017-0194-z

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.
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.
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.