Cytokine gene polymorphism in kidney transplantation — Impact of TGF-β1, TNF-α and IL-6 on graft outcome

Nikolova, Penka N.; Ivanova, Milena; Mihailova, Snezhina; Myhailova, Anastassia P.; Baltadjieva, Daniela; Simeonov, Petar; Paskalev, E.; Naumova, Elissaveta

doi:10.1016/j.trim.2007.10.003

Cited by 44 publications

(29 citation statements)

References 33 publications

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“…In the present study, LTS patients did not show increased TGF-␤ gene expression, indicating that the suggested Treg-mediated immunoregulation in our patients was TGF-␤ independent. Moreover, the highest TGF-␤ transcripts were found in ChrRx patients, which is in line with the hypothesis that TGF-␤ plays an important role in the pathogenesis of ChrRx or chronic allograft nephropathy (CAN), leading to collagen dependent fibrosis (17,18). Although the involvement of TGF-␤ in the development of CAN has been attributed to the chronic use of CNI, we could not substantiate this in our study because all ChrRx patients in our study, including those who did not receive CNI, showed augmented expression of TGF-␤.…”

Section: Discussionsupporting

confidence: 84%

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Expression of Regulatory T–Cell-Related Molecule Genes and Clinical Outcome in Kidney Transplant Recipients

Álvarez¹,

Opelz²,

García³

et al. 2009

Transplantation

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Our results suggest that high expression of FOXP3 and chemokine receptor genes in LTS patients are possible indicators of a regulatory process that contributes to long-term allograft acceptance. Markers that were increased in LTS patients were found to be decreased in ChrRx patients, suggesting that rejection may partly be the result of a lack of this regulatory process. FOXP3 and CCR7 and CXCR4 transcripts might be used as markers to distinguish patients who developed long-term allograft acceptance from patients who are prone to ChrRx.

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Section: Discussionsupporting

confidence: 84%

“…2A-C), in agreement with previous reports (17,18), we found a significantly higher TGF-␤ transcript level in ChrRx patients than in LTS patients, patients on dialysis, and HC (PϽ0.01, PϽ0.01, and PϽ0.001, respectively) (Fig. 2D).…”

Section: Tgf-␤ Expression Is Increased In Chrrx Patientssupporting

confidence: 93%

Expression of Regulatory T–Cell-Related Molecule Genes and Clinical Outcome in Kidney Transplant Recipients

Álvarez¹,

Opelz²,

García³

et al. 2009

Transplantation

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“…While codon 25 SNP have been consistently associated with decreased plasma levels, 17,18 conflicting data have been published regarding the impact of codon 10 SNP on plasma levels of TGF-β1. [17][18][19][20][21][22] These polymorphisms have been associated with an increased incidence of breast and colorectal neoplasia 20,23 and worse outcome following solid organ transplantation 24 and sibling HSCT. 5,25,26 To date there is no published evidence on the possible role of these SNP in unrelated donor HSCT, or on plasma TGF-β1 levels and clinical outcomes following transplantation.…”

Section: Introductionmentioning

confidence: 99%

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Berro¹,

Mayor²,

Maldonado-Torres³

et al. 2009

Haematologica

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BackgroundMany genetic factors play major roles in the outcome of hematopoietic stem cell transplants from unrelated donors. Transforming growth factor β1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes. Design and MethodsWe investigated the impact of single nucleotide polymorphisms at codons 10 and 25 of TGFB1, the gene encoding for transforming growth factor β1, on outcomes in 427 myeloablative-conditioned transplanted patients. In addition, transforming growth factor β1 plasma levels were measured in 263 patients and 327 donors. ResultsPatients homozygous for the single nucleotide polymorphism at codon 10 had increased non-relapse mortality (at 3 years: 46.8% versus 29.4%, P=0.014) and reduced overall survival (at 5 years 29.3% versus 42.2%, P=0.013); the differences remained statistically significant in multivariate analysis. Donor genotype alone had no impact, although multiple single nucleotide polymorphisms within the pair were significantly associated with higher non-relapse mortality (at 3 years: 44% versus 29%, P=0.021) and decreased overall survival (at 5 years: 33.8% versus 41.9%, P=0.033). In the 10/10 HLA matched transplants (n=280), recipients of non-wild type grafts tended to have a higher incidence of acute graft-versus-host disease grades II-IV (P=0.052). In multivariate analysis, when analyzed with patients' genotype, the incidences of both overall and grades II-IV acute graft-versushost disease were increased (P=0.025 and P=0.009, respectively) in non-wild-type pairs. ConclusionsWe conclude that increasing numbers of single nucleotide polymorphisms in codon 10 of TGFB1 in patients and donors are associated with a worse outcome following hematopoietic stem cell transplantation from unrelated donors.Key words: stem cell transplantation, TGF-β1, polymorphisms, survival, graft-versus-host disease.Citation: Berro M, Mayor NP, Maldonado-Torres H, Cooke L, Kusminsky G, Marsh SGE, Madrigal JA, and Shaw BE. Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation. Haematologica. 2010; 95:276-283. doi:10.3324/haematol.2009 This is an open-access paper.Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

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“…The exception is TNFA rs1800629 (−308). Associations have been found between this SNP and numerous outcomes in donors and recipients: acute rejection, recipients [21,44,46,[58][59][60][61][62][63]; graft survival, recipients [27,64]; graft survival, donors [65]; associations in sub group analyses, recipients [66][67][68], associations in sub group analyses, donors [49]; associations with other phenotypes/multiple phenotypes [69][70][71][72]; donors: [73] (see Table 2). …”

Section: Notable Associations: Tnfa Rs1800629 (−308)mentioning

confidence: 99%

Genetic polymorphisms in the immune response: A focus on kidney transplantation

Stojanova

Pouché

Picard

2016

Clinical Biochemistry

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Cytokine gene polymorphism in kidney transplantation — Impact of TGF-β1, TNF-α and IL-6 on graft outcome

Cited by 44 publications

References 33 publications

Expression of Regulatory T–Cell-Related Molecule Genes and Clinical Outcome in Kidney Transplant Recipients

Expression of Regulatory T–Cell-Related Molecule Genes and Clinical Outcome in Kidney Transplant Recipients

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Genetic polymorphisms in the immune response: A focus on kidney transplantation

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