title: HLA Associations and Risk of Posttransplant Lymphoproliferative Disorder in a Danish Population-Based Cohort.
abstract: BACKGROUND
  Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell-depleting induction therapy and primary infection or reactivation of Epstein-Barr virus. Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting.
  
  
  METHODS
  We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database. Having identified 93 PTLD patients in the cohort, we investigated the association of HLA types with PTLD, Epstein-Barr virus status and time to PTLD onset. The outcomes survival and PTLD were evaluated using Cox regression; mismatching, and the PTLD-specific mortality were evaluated in a competing risk analysis.
  
  
  RESULTS
  Risk of PTLD was associated with male sex (odds ratio, 1.70; 95% confidence interval, 1.07-2.71), and, in women, HLA-DR13 conferred an increased risk (odds ratio, 3.22; 95% confidence interval, 1.41-7.31). In multivariate analysis, HLA-B45 and HLA-DR13 remained independent predictive factors of PTLD. Mismatching in the B locus was associated with a reduced risk of PTLD (P < 0.001). Overall survival was poor after a PTLD diagnosis and was significantly worse than that in the remaining transplant cohort (P < 0.001).
  
  
  CONCLUSIONS
  Our data indicate risk-modifying HLA associations, which can be clinically useful after transplantation in personalized monitoring schemes. Given the strong linkage disequilibrium in the HLA region, the associations must be interpreted carefully. The large size, virtually complete ascertainment of cases and no loss to follow-up remain important strengths of the study.
authors: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors: Maja Ølholm
authors: MØ
authors: Vase
authors: Department of Nephrology, Aarhus University Hospital, Aarhus, Denmark.
authors: Eva Futtrup
authors: EF
authors: Maksten
authors: Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark.
authors: Charlotte
authors: C
authors: Strandhave
authors: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors: Esben
authors: E
authors: Søndergaard
authors: Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors: Knud
authors: K
authors: Bendix
authors: Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors: Stephen
authors: S
authors: Hamilton-Dutoit
authors: Department of Pathology, Copenhagen University Hospital, København, Denmark.
authors: Claus
authors: C
authors: Andersen
authors: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors: Michael Boe
authors: MB
authors: Møller
authors: Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, København, Denmark.
authors: Søren Schwartz
authors: SS
authors: Sørensen
authors: Department of Nephrology, Odense University Hospital, Odense, Denmark.
authors: Jan
authors: J
authors: Kampmann
authors: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Hans
authors: H
authors: Eiskjær
authors: Division of Lung Transplantation, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors: Martin
authors: M
authors: Iversen
authors: Scandiatransplant, Aarhus University Hospital, Aarhus, Denmark.
authors: Ilse Duus
authors: ID
authors: Weinreich
authors: Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
authors: Bjarne
authors: B
authors: Møller
authors: Department of Nephrology, Aarhus University Hospital, Aarhus, Denmark.
authors: Bente
authors: B
authors: Jespersen
authors: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors: Francesco
authors: F
authors: d'Amore