Nonimmunologic complications and gene polymorphisms of immunoregulatory cytokines in long-term renal transplants

Babel, Nina; Черепнев, Г. В.; Kowalenko, Alexander; Hörstrup, Jan; Volk, Hans‐Dieter; Reinke, Petra

doi:10.1111/j.1523-1755.2004.00749.x

Cited by 26 publications

(17 citation statements)

References 30 publications

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“…These two chronic diseases have been previously recognized as risk factors for DHF in Cubans [6]. Cytokines genes polymorphism has been associated with other viral infections outcome [42][43][44][45].…”

Section: Discussionmentioning

confidence: 97%

Tumor necrosis factor–alpha, transforming growth factor–β1, and interleukin-10 gene polymorphisms: implication in protection or susceptibility to dengue hemorrhagic fever

et al. 2010

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Section: Discussionmentioning

confidence: 97%

Tumor necrosis factor–alpha, transforming growth factor–β1, and interleukin-10 gene polymorphisms: implication in protection or susceptibility to dengue hemorrhagic fever

et al. 2010

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“…Cytokines have been shown to be implicated in the occurrence of AR of renal allografts, with different subtypes of cytokines having controversial effects (Azarpira et al, 2009). Cytokine gene polymorphisms have been associated with the development of both immunological and nonimmunological complications after renal transplantation (Babel et al, 2004). Cytokine production is associated with a risk of postoperative organ dysfunction as well as increased morbidity and mortality (Hadimioglu et al, 2012).…”

Section: Discussionmentioning

confidence: 98%

Genetic association of interleukin‐2, interleukin‐4, interleukin‐6, transforming growth factor‐β, tumour necrosis factor‐α and blood concentrations of calcineurin inhibitors in Turkish renal transplant patients

Seyhun

Çiftçi

Kekik

et al. 2015

Int J Immunogenetics

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Cytokines are essential for the control of the immune response as most of the immunosuppressive drugs target cytokine production or their action. The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are immunosuppressive drugs widely used after renal transplantation to prevent allograft rejection. They are characterized by large interindividual variability in their pharmacokinetics; therefore, monitoring their blood concentrations is important to predict their optimal dosage following transplantation. Calcineurin inhibitors inhibit the phosphatase activity of calcineurin, thereby suppressing the production of other cytokines such as transforming growth factor (TGF-β), tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-2, and IL-4. The aim of this study was to investigate the relationship between polymorphisms of cytokines and blood concentrations of CNIs in renal transplant patients. The study included 53 CsA-treated renal transplant patients and 37 tacrolimus-treated renal transplant patients. Cytokine polymorphisms were analysed using polymerase chain reaction (PCR) sequence-specific primers with the cytokine CTS-PCR-sequence-specific primers Tray Kit; University of Heidelberg. Blood concentrations of CNIs were determined with Cloned Enzyme Donor Immunoassay (CEDIA) method. Patients with TC genotype of TGF-β at codon 10 had lower CsA blood concentrations than the TT and CC genotypes (P = 0.005) at 1 month in CsA treatment group. The ratio of blood concentration/dose of CsA for patients with TGF-β1-codon 10 TC genotype was lower than for patients with TT, CC genotypes, and the dose given to these patients was higher in the first month (P = 0.046). The ratio of blood concentration/dose of CsA for patients with IL-2-330 GG genotype was higher than for patients with GT, TT genotypes, and the dose given to these patients was lower at first month and sixth months (P = 0.043, P = 0.035 respectively). The tacrolimus blood concentrations were significantly higher in patients with the genotype GG of IL-2-330 (P = 0.012) at the third month. Patients who had the TC genotype TGF-β codon 10 had lower CsA blood concentrations and this group had higher acute rejection (P = 0.033). These results suggest that the genotyping for TGF-β-codon 10, IL-2-330 and IL-6-174 polymorphisms may help individualized immunosuppressive dosage regiments.

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“…The TGF-β1 cytokine concentration is likely higher in nephritis, which nephritis is one of the mortality causes in Lupus patients [4]. Furthermore, the increasing of TGF-β1 production may be projected to the severity of Lupus Nephritis [4, 5]. Another study showed that G915C polymorphism of TGFB1 gene is related to the progression of liver fibrosis in patients with chronic Hepatitis C [6].…”

Section: Introductionmentioning

confidence: 99%

The Potential effect of G915C polymorphism in regulating TGF-β1 transport into Endoplasmic Reticulum for cytokine production

et al. 2014

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The TGF-β1 cytokine concentration is known to be higher in nephritis with implied Lupus Nephritis severity. The production of TGF-β1 cytokine is associated with G915C polymorphism. Therefore, it is of interest to study G915C polymorphism. The G915C polymorphism changes codon 25 which encodes arginine into proline in the signal peptide of TGF-β1. The amino acid substitution affects signal peptide properties that may inhibit the transport of TGF-β1 into the endoplasmic reticulum and eventually decline the cytokine production. Hence, the effect of G915C polymorphism on the properties of the signal peptide, the ability of TGF-β1 transport into the endoplasmic reticulum and the concentrations of urinary TGF-β1 in Lupus Nephritis patients was studied. The arginine substitution into proline decreased the polarity of the signal peptide for TGF-β1. The increased hydrophobicity with increased binding energy of the signal peptide for TGF-β1 to Signal Recognition Particle (SRP) and translocon is shown. This implies decreased protein complex stability in potentially blocking the transport of TGF-β1 into the endoplasmic reticulum. This transport retention possibly hampers the synthesis and maturation of TGF-β1 leading to decreased cytokine production.

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Nonimmunologic complications and gene polymorphisms of immunoregulatory cytokines in long-term renal transplants

Cited by 26 publications

References 30 publications

Tumor necrosis factor–alpha, transforming growth factor–β1, and interleukin-10 gene polymorphisms: implication in protection or susceptibility to dengue hemorrhagic fever

Tumor necrosis factor–alpha, transforming growth factor–β1, and interleukin-10 gene polymorphisms: implication in protection or susceptibility to dengue hemorrhagic fever

Genetic association of interleukin‐2, interleukin‐4, interleukin‐6, transforming growth factor‐β, tumour necrosis factor‐α and blood concentrations of calcineurin inhibitors in Turkish renal transplant patients

The Potential effect of G915C polymorphism in regulating TGF-β1 transport into Endoplasmic Reticulum for cytokine production

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