title: Pretransplant CD8 T-cell response to IE-1 discriminates seropositive kidney recipients at risk of developing CMV infection posttransplant.
abstract: BACKGROUND
  Cytomegalovirus (CMV) infection is an ongoing clinical problem in solid-organ transplantation (SOT). Pretransplant CMV serology is currently the only tool for assessing the risk of CMV infection, although cellular immune responses driven by CMV-specific CD4 and CD8 T lymphocytes are important for controlling viral replication. Therefore, the analysis of CMV-specific T cells may be useful for estimating the risk of infection.
  
  
  METHODS
  This is a prospective study of patients with kidney transplants and no prophylactic treatment for CMV replication. CD4 and CD8 T-cell responses to the major CMV pp65 and IE-1 antigens in 15 seropositive patients at intermediate risk of CMV infection were investigated, according to current algorithms. Intracellular flow cytometry was employed to determine IFN-γ production as a functional readout. The response was analyzed in pretransplant samples and prospectively at 1 and 6 months and at 1 year posttransplant.
  
  
  RESULTS
  It was observed that the CD8 responses to IE-1 antigen were practically absent pretransplant in patients who developed CMV infection posttransplant. Within the group of patients free of infection, CD8 responses to IE-1 were detected more frequently and were significantly higher (P=0.0083). In a receiver operating characteristics curve analysis (AUC=0.929; P=0.010; 95% CI: 0.078-1.0), low CD8 responses to IE-1 (≤0.05%) pretransplant predicted the development of CMV infection under the immunosuppressive regime after transplant with 100% specificity and 85.7% sensitivity.
  
  
  CONCLUSIONS
  Assessment of IE-1-specific CD8 T-cell frequencies pretransplant may be a useful tool for identifying seropositive SOT patients at risk of developing CMV infection posttransplant.
authors.affiliation: 1 Nephrology Service, University Hospital La Paz, Madrid, Spain. 2 Health Research Institute, University Hospital La Paz-IdiPAZ, Madrid, Spain. 3 Address correspondence to: Teresa Bellón, Health Research Institute, University Hospital La Paz-IdiPAZ, Paseo Castellana 261, Madrid, Spain.
authors.forename: Maria Ovidia
authors.initials: MO
authors.lastname: López-Oliva
authors.forename: Virginia
authors.initials: V
authors.lastname: Martinez
authors.forename: Agueda
authors.initials: A
authors.lastname: Buitrago
authors.forename: Carlos
authors.initials: C
authors.lastname: Jiménez
authors.forename: Begoña
authors.initials: B
authors.lastname: Rivas
authors.forename: Fernando
authors.initials: F
authors.lastname: Escuin
authors.forename: María José
authors.initials: MJ
authors.lastname: Santana
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.forename: Teresa
authors.initials: T
authors.lastname: Bellón
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016030:Kidney Transplantation / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D057234:Preoperative Period; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000939:Epitopes; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma