title: Post-transplantation lymphoproliferative disease: Epstein-Barr virus DNA levels, HLA-A3, and survival.
abstract: BACKGROUND
  Elevation in Epstein-Barr virus (EBV) circulating DNA has been proposed as a marker for development of post-transplant lymphoproliferative disease (PTLD), but few published data exist in the study of lung-transplant recipients.
  
  
  OBJECTIVE
  To determine if elevated EBV DNA levels, in combination with other risk factors, were predictive of PTLD.
  
  
  METHODS
  We conducted a retrospective, single-center study examining all lung transplant recipients (n = 296) and EBV DNA levels (n = 612) using real-time TaqMan polymerase chain reaction. There were 13 cases of PTLD overall, of which 5 occurred in the era of EBV DNA monitoring.
  
  
  RESULTS
  EBV DNA levels were distributed differently among seropositive and seronegative patients, with the latter having higher values (P < 0.0001). Among the cohort of pretransplantation seropositive patients, there was one diagnosed with PTLD. The EBV DNA level in this patient was elevated at the time of PTLD diagnosis (sensitivity = 100%, specificity = 100% for PTLD). Among the cohort of pretransplantation seronegative patients, there were four with a diagnosis of PTLD. In all four patients, the EBV DNA level was detectable (sensitivity = 100%, specificity = 24%), but in only two was it elevated (sensitivity = 50%, specificity = 22%). HLA-A3 expression in the recipient and/or donor conferred additional risk for PTLD among the seronegative patients (P = 0.026 to 0.003). No other PTLD risk factor was found.
  
  
  CONCLUSIONS
  EBV DNA levels are a useful but imperfect predictor of PTLD in patients with lung transplants. Pretransplant EBV status affected the results of the assay and should be considered when interpreting test results. HLA-A3 was strongly linked to PTLD and may be a novel marker of PTLD risk.
authors.affiliation: The School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wheless
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Gulley
authors.forename: Nancy
authors.initials: N
authors.lastname: Raab-Traub
authors.forename: Patrick
authors.initials: P
authors.lastname: McNeillie
authors.forename: Isabel P
authors.initials: IP
authors.lastname: Neuringer
authors.forename: Hubert J
authors.initials: HJ
authors.lastname: Ford
authors.forename: Robert M
authors.initials: RM
authors.lastname: Aris