Evidence for Genetic Susceptibility Towards Development of Posttransplant Lymphoproliferative Disorder in Solid Organ Recipients

Babel, Nina; Vergopoulos, Athanasios; Trappe, Ralf Ulrich; Oertel, Stephan; Hammer, Markus; Karaivanov, Stoyan; Schneider, Natália; Riess, Hanno; Papp-Váry, Matthias; Neuhaus, R.; Gondek, Lukasz P.; Volk, Hans‐Dieter; Reinke, Petra

doi:10.1097/01.tp.0000269617.60751.c4

Cited by 50 publications

(39 citation statements)

References 22 publications

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“…20 Babel et al have found increased risk of posttransplant lymphoma in solid organ recipients with TGFβ1 +915CC genotype. 10 Mazur et al reported that +915GG genotype was associated with two or more extranodal involvement in non-Hodgkin's lymphoma patients.…”

Section: Discussionmentioning

confidence: 99%

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Association of TGF-1 Gene (+915G>C) Polymorphism with Chronic Lymphocytic Leukemia

Yunus¹,

Yılmaz²,

Çebi³

et al. 2015

UHOD

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TGFβ1 is an important cytokine acts as an antiinflammatory agent, and inhibits B cell proliferation. In patients with chronic lymphocytic leukemia (CLL), serum level of TGFβ1 are found elevated. Presence of G allele at position +915 in TGFβ1 gene results in arginine synthesis which is associated with higher expression of TGFβ1. We investigated the association of TGFβ1 +915G>C polymorphism with predisposition, clinical characteristics and laboratory findings of CLL. 50 CLL patients and 50 healthy controls were included in this study. Genotypes were determined by PCR-RFLP method. We couldn't find statistically significant differences between patient and control groups in terms of genotype distributions and allele frequencies. However, GC genotype frequency was slightly higher in CLL patients than healthy controls. hastalarında ilginç olarak TGFβ1 serum seviyeleri artmış olarak saptanmıştır. TGFβ1 (+915G>C) polimorfizminde Arjinin aminoasidi ile ilişkili olan G alleli varlığında TGFβ1 ekspresyonu artmış olarak saptanmaktadır. Bu çalışmada TGFβ1 (+915G>C) polimorfizminin KLL hastalığına yatkınlık, klinik özellikler ve laboratuar bulguları ile ilişkisi incelenmiştir. Çalışmaya KLL tanısı almış 50 hasta birey ve sağlıklı kontrol grubu olarak 50 gönüllü birey dahil edilmiştir. TGFβ1 (+915G>C) genotipleri PCR-RFLP metodu ile belirlenmiştir. Çalışma sonucunda hasta grup ile sağlıklı kontrol grubu arasında genotip dağılımı ve allel frekansı açısından anlamlı bir fark saptanmamıştır. Bununla birlikte KLL hastalarında GC genotipi, istatistiksel olarak anlamlı olmasa da, kontrol grubuna göre daha fazla görülmüştür. Ayrıca TGFβ1 +915GC genotipi ile trizomi 12 varlığı arasında anlamlı bir ilişki saptanmıştır (p= 0.007). TGFβ1 +915G>C polimorfizmi ile trizomi 12 ve KLL arasındaki ilişkiyi açıklamak için başka çalışmalara da ihtiyaç vardır.

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Section: Discussionmentioning

confidence: 99%

“…TGFβ1 polymorphisms were found associated with several malignencies. [10][11][12][13] TGFβ1 +915G>C polymorphism localised to the first exon leads to the Arginine(Arg)-Proline(Pro) substitution at codon 25. +915G allele involving Arg aminoacide is associated with higher expression of TGFβ1.…”

Section: -8mentioning

confidence: 99%

Association of TGF-1 Gene (+915G>C) Polymorphism with Chronic Lymphocytic Leukemia

Yunus¹,

Yılmaz²,

Çebi³

et al. 2015

UHOD

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“…It is suggested that HLA type influences the immune system's ability to present certain foreign epitopes for immune destruction. Recently, there is increased acknowledgment of the role of host cytokine polymorphisms (e.g., mutated gamma interferon [IFN-␥], transforming growth factor ␤ [TGF-␤], and interleukin-10 [IL-10]) in defense against EBV and other viral pathogens (13,80,108,179). Likewise, EBV genomic polymorphism is emerging as a potential contributor to tumorigenesis (51,74,118,165,199).…”

Section: Risk Factors For Ptldmentioning

confidence: 99%

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

2010

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SUMMARYEpstein-Barr virus (EBV) DNA measurement is being incorporated into routine medical practice to help diagnose, monitor, and predict posttransplant lymphoproliferative disorder (PTLD) in immunocompromised graft recipients. PTLD is an aggressive neoplasm that almost always harbors EBV DNA within the neoplastic lymphocytes, and it is often fatal if not recognized and treated promptly. Validated protocols, commercial reagents, and automated instruments facilitate implementation of EBV load assays by real-time PCR. When applied to either whole blood or plasma, EBV DNA levels reflect clinical status with respect to EBV-related neoplasia. While many healthy transplant recipients have low viral loads, high EBV loads are strongly associated with current or impending PTLD. Complementary laboratory assays as well as histopathologic examination of lesional tissue help in interpreting modest elevations in viral load. Circulating EBV levels in serial samples reflect changes in tumor burden and represent an effective, noninvasive tool for monitoring the efficacy of therapy. In high-risk patients, serial testing permits early clinical intervention to prevent progression toward frank PTLD. Restoring T cell immunity against EBV is a major strategy for overcoming PTLD, and novel EBV-directed therapies are being explored to thwart virus-driven neoplasia.

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“…One theory is that the transplanted organ (a common site of lymphoma involvement) is subject to frequent subclinical rejection that might induce a state of chronic antigen stimulation that contributes to a tumorigenic environment (34). The predilection for other extranodal sites suggests a requirement for specific external stimuli, such as cytokines, and polymorphisms in anti-inflammatory cytokines are associated with susceptibility to PTLD (35). A total of 5 noncoding region mutations of the BCL6 gene are frequent and are associated with monomorphic histology and an aggressive clinical outcome.…”

Section: Role Of Nonviral Factors In Ptld Pathogenesismentioning

confidence: 99%

Epstein–Barr Virus-Related Post-Transplant Lymphoproliferative Disorders: Pathogenetic Insights for Targeted Therapy

Nourse

Jones

Gandhi

2011

American Journal of Transplantation

124

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Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of major, life-threatening lymphoproliferative diseases occurring in the post-transplant setting. The majority of PTLD is of B-cell origin and is associated with several risk factors, the most significant being Epstein-Barr virus (EBV) infection. EBV's in vitro transforming abilities, distinctive latency, clonality within the malignant cells and response to targeted therapies implicate a critical role in the biology of PTLD. This minireview focuses on EBV-related PTLD pathogenesis, in particular the interplay between aspects of the EBV life cycle and latency with nonviral factors resulting in the wide spectrum of histology and clinical presentations encountered in PTLD. With the increased prevalence of transplantation a rise in the incidence of PTLD may be expected. Therefore the importance of laboratory and animal models in the understanding of PTLD and the development of novel therapeutic approaches is discussed.

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Evidence for Genetic Susceptibility Towards Development of Posttransplant Lymphoproliferative Disorder in Solid Organ Recipients

Abstract: 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.

Cited by 50 publications

References 22 publications

Association of TGF-1 Gene (+915G>C) Polymorphism with Chronic Lymphocytic Leukemia

Association of TGF-1 Gene (+915G>C) Polymorphism with Chronic Lymphocytic Leukemia

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

Epstein–Barr Virus-Related Post-Transplant Lymphoproliferative Disorders: Pathogenetic Insights for Targeted Therapy

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