title: Preformed frequencies of cytomegalovirus (CMV)-specific memory T and B cells identify protected CMV-sensitized individuals among seronegative kidney transplant recipients.
abstract: BACKGROUND
  Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers.
  
  
  METHODS
  We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG-seronegative (sR(-)) and 86 CMV IgG-seropositive (sR(+)) patients. Clinical outcome was evaluated in both groups.
  
  
  RESULTS
  All sR(+) patients showed a wide range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell frequencies were also clearly detected in 30% of sR(-) patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test.
  
  
  CONCLUSIONS
  Assessment of CMV-specific memory T- and B-cell responses before kidney transplantation among sR(-) recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection.
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute.
authors.forename: Marc
authors.initials: M
authors.lastname: Lúcia
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute.
authors.forename: Elena
authors.initials: E
authors.lastname: Crespo
authors.affiliation: Renal Transplant Unit, Nephrology Department.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Melilli
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute Renal Transplant Unit, Nephrology Department.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Cruzado
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute.
authors.forename: Sergi
authors.initials: S
authors.lastname: Luque
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute.
authors.forename: Inés
authors.initials: I
authors.lastname: Llaudó
authors.affiliation: Microbiology Department.
authors.forename: Jordi
authors.initials: J
authors.lastname: Niubó
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute Renal Transplant Unit, Nephrology Department.
authors.forename: Joan
authors.initials: J
authors.lastname: Torras
authors.affiliation: Infectious Disease Department, Bellvitge University Hospital, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Fernandez
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute Renal Transplant Unit, Nephrology Department.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute Renal Transplant Unit, Nephrology Department.
authors.forename: Oriol
authors.initials: O
authors.lastname: Bestard
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000517:prevention & control*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology
chemical_list: D007371:Interferon-gamma
keywords: CMV infection; T- and B-cell ELISPOT assay; adaptive immunity; kidney transplantation