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HLA associations and risk of posttransplant lymphoproliferative disorder in Danish population-based cohort

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  • Maja Ølholm Vase
  • Eva Futtrup Maksten, Department of Nephrology, Aarhus University Hospital, Institute of Clinical Medicine, Danmark
  • Charlotte Strandhave, Aalborg University Hospital, Institue of Clinical Medicine, Aalborg, Danmark
  • Esben Søndergaard
  • Knud Bendix, Danmark
  • Stephen Jacques Hamilton Dutoit
  • Claus Andersen, Københavns Universitet, Danmark
  • Michael Boe Møller, Department of Pathology, Odense University Hospital, Odense, Danmark
  • Søren Schwartz Sørensen, Department of Nephrology, Rigshospitaltet, Copenhagen University Hospital, Copenhagen, Danmark
  • Jan Kampmann, Department of Nephrology, Odense University Hospital, Odense, Danmark
  • Hans Eiskjær
  • Martin Iversen, Rigshospitalet, Danmark
  • Ilse Duus Weinreich
  • Bjarne Møller
  • Bente Jespersen
  • Francesco Annibale D'Amore
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.
OriginalsprogEngelsk
TidsskriftTransplantation Direct
Vol/bind1
Nummer7
Sider (fra-til)p e25
ISSN2373-8731
DOI
StatusUdgivet - aug. 2015

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