Evidence for genetic susceptibility towards development of posttransplant lymphoproliferative disorder in solid organ recipients

Nina Babel, Athanasios Vergopoulos, Ralf Ulrich Trappe, Stephan Oertel, Markus H. Hammer, Stoyan Karaivanov, Natalia Schneider, Hanno Riess, Matthias Papp-Vary, Ruth Neuhaus, Lukasz Pawel Gondek, Hans Dieter Volk, Petra Reinke

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication after organ transplantation. The identification of risk factors for PTLD development is important for disease management. It has been shown that cytokine gene polymorphisms are associated with lymphoma and Epstein-Barr virus (EBV)-associated diseases in nonimmunosuppressed patients. In the present case-control study, we analyzed the impact of -1082 interleukin (IL)-10, -308 tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 (codon 10, 25), and +874 interferon (IFN)-γ gene single-nucleotide polymorphisms on the late onset EBV-associated PTLD. METHODS. Out of 1,765 solid organ recipients, 38 patients with late-onset EBV-associated PTLD and 408 matched solid organ recipients were selected and enrolled in the study. Single nucleotide polymorphisms (SNPs) for -1082IL-10, -308TNF-α, TGF-β1 (codon 10, 25), and +874IFN-γ genes were analyzed by a sequence specific primer polymerase chain reaction and were related to the PTLD development, and the disease course and outcome. RESULTS. The TGF-β1 (codon 25) GG genotype was detected more frequently in controls than in PTLD patients (odds ratio=0.34, 95% confidence interval: 0.17-0.69, P=0.0022). The frequency of -1082 IL-10 GG genotype was also significantly higher in controls than in PTLD patients (odds ratio=0.5, 95% confidence interval: 0.25-1.0, P=0.044). There were no associations between -308TNF-α, TGF-β1 codon 10, and +874IFN-γ SNPs and PTLD. Disease course and outcome were not associated with any cytokine SNPs. CONCLUSIONS. Polymorphisms in two key anti-inflammatory cytokines, IL-10 and TGF-beta, are associated with susceptibility to EBV-associated PTLD, suggesting that a shift in pro-/anti-inflammatory response is involved in the pathogenesis of PTLD.

Original languageEnglish (US)
Pages (from-to)387-391
Number of pages5
JournalTransplantation
Volume84
Issue number3
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

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Keywords

  • Cytokine
  • Epstein-Barr virus
  • Posttransplant lymphoproliferative disorder
  • Single nucleotide polymorphism
  • Transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Babel, N., Vergopoulos, A., Trappe, R. U., Oertel, S., Hammer, M. H., Karaivanov, S., Schneider, N., Riess, H., Papp-Vary, M., Neuhaus, R., Gondek, L. P., Volk, H. D., & Reinke, P. (2007). Evidence for genetic susceptibility towards development of posttransplant lymphoproliferative disorder in solid organ recipients. Transplantation, 84(3), 387-391. https://doi.org/10.1097/01.tp.0000269617.60751.c4