title: Validation of T-Track® CMV to assess the functionality of cytomegalovirus-reactive cell-mediated immunity in hemodialysis patients.
abstract: 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.
authors.affiliation: Department of Nephrology, University Medical Center Regensburg, Regensburg, Germany. Bernhard.Banas@ukr.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Banas
authors.affiliation: Department of Nephrology, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Böger
authors.affiliation: Dialysis Center Landshut, Landshut, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Lückhoff
authors.affiliation: 5th Department of Medicine, University Medical Center Mannheim, Medical Faculty Mannheim of the University Heidelberg, Mannheim, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Krüger
authors.affiliation: Lophius Biosciences GmbH, Regensburg, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Barabas
authors.affiliation: Lophius Biosciences GmbH, Regensburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Batzilla
authors.affiliation: Lophius Biosciences GmbH, Regensburg, Germany.|Institute of Clinical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Schemmerer
authors.affiliation: Institute of Clinical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Köstler
authors.affiliation: Lophius Biosciences GmbH, Regensburg, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Bendfeldt
authors.affiliation: Lophius Biosciences GmbH, Regensburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Rascle
authors.affiliation: Institute of Clinical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Lophius Biosciences GmbH, Regensburg, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Deml
authors.affiliation: Dialysis Center Schwandorf, Schwandorf, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Leicht
authors.affiliation: 5th Department of Medicine, University Medical Center Mannheim, Medical Faculty Mannheim of the University Heidelberg, Mannheim, Germany.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D002478:Cells, Cultured; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000276:immunology; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D007111:Immunity, Cellular; D007118:Immunoassay; D016867:Immunocompromised Host; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods; D015588:Observer Variation; D010750:Phosphoproteins / Q000276:immunology; D006435:Renal Dialysis; D012680:Sensitivity and Specificity; D014763:Viral Matrix Proteins / Q000276:immunology; D014850:Waiting Lists
chemical_list: D000914:Antibodies, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa
keywords: CMV; Cell-mediated immunity; Cytomegalovirus; Hemodialysis; IE-1; IFN-γ ELISpot; QuantiFERON®-CMV; T-Track® CMV; iTAg™ MHC Tetramers; pp65