Evidence for genetic susceptibility towards development of posttransplant lymphoproliferative disorder in solid organ recipients.
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)-alpha, transforming growth factor (TGF)-beta1 (codon 10, 25), and +874 interferon (IFN)-gamma 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-alpha, TGF-beta1 (codon 10, 25), and +874IFN-gamma 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-beta1 (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-alpha, TGF-beta1 codon 10, and +874IFN-gamma 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.
Babel
Nina
N
Department of Nephrology, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany. nina.babel@charite.de
Vergopoulos
Athanasios
A
Trappe
Ralf Ulrich
RU
Oertel
Stephan
S
Hammer
Markus H
MH
Karaivanov
Stoyan
S
Schneider
Natalia
N
Riess
Hanno
H
Papp-Vary
Matthias
M
Neuhaus
Ruth
R
Gondek
Lukasz Pawel
LP
Volk
Hans-Dieter
HD
Reinke
Petra
P
D000328:Adult; D016022:Case-Control Studies; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma