title: Simultaneous monitoring of cytomegalovirus-specific antibody and T-cell levels in seropositive heart transplant recipients.
abstract: OBJECTIVE
  Human cytomegalovirus (CMV) active infection (CMV infection) poses serious risks to CMV-seropositive heart transplant recipients. We evaluated the usefulness of simultaneous assessment of CMV-specific values for parameters of the humoral (antibodies) and cellular (CD4+ and CD8+ T-cells) immune responses in the identification of heart recipients at risk of developing CMV infection after transplantation.
  
  
  METHODS
  We prospectively studied 38 CMV-seropositive heart recipients. Anti-CMV antibody titers were assessed using enzyme-linked immunosorbent assays. CD4+ and CD8+ T-cell responses to overlapping peptide pools of the CMV proteins pp65 and immediate early protein-1 (IE1) were evaluated by flow cytometry. Immunological studies were performed before transplantation and at 30 days after transplantation. Patients with CMV infection were compared with heart recipients without CMV infection.
  
  
  RESULTS
  During the 6-month follow-up period, 13 (34.2%) patients developed CMV infection. At baseline, the mean anti-CMV-IgG antibody titer was lower in patients who developed CMV infection. This difference remained at 30 days after transplantation. One month after transplantation, the mean percentage of IE1-specific CD8+ T cells that are IFNg-positive (CD8/IFNg + IE1) was lower in CMV-infected patients. The predictive value of these variables at 30 days was increased when they were combined. Cox regression analysis revealed an association between the risk of developing CMV infection and the combination marker (low anti-CMV titer [<16,100] and low CD8/IFNg + IE1 percentages [<0.40%], relative hazard, 6.07; p = 0.019). The combination marker remained significant after adjustment for clinical variables.
  
  
  CONCLUSIONS
  This novel approach of a simultaneous assessment of specific anti-CMV antibody titers and CD8/IFNg + IE1 percentages might help identify heart transplant recipients with an increased risk of developing CMV infection.
authors.affiliation: Transplant Immunology Group, Clinical Immunology Department, Gregorio Marañón Hospital, Dr Esquerdo 46, 28007, Madrid, Spain. jcarbone.hgugm@salud.madrid.org
authors.forename: Javier
authors.initials: J
authors.lastname: Carbone
authors.forename: Nallibe
authors.initials: N
authors.lastname: Lanio
authors.forename: Antonio
authors.initials: A
authors.lastname: Gallego
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
authors.forename: Joaquin
authors.initials: J
authors.lastname: Navarro
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.forename: Roberto
authors.initials: R
authors.lastname: Alonso
authors.forename: Pilar
authors.initials: P
authors.lastname: Catalán
authors.forename: Juan
authors.initials: J
authors.lastname: Fernández-Yáñez
authors.forename: Jesús
authors.initials: J
authors.lastname: Palomo
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruiz
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández-Cruz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sarmiento
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood / Q000276:immunology; D014763:Viral Matrix Proteins / Q000097:blood / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa