Differential Regulation of the Nuclear Factor-κB Pathway by Rabbit Antithymocyte Globulins in Kidney Transplantation

Urbanová, Marie; Brabcova, Irena; Girmanova, Eva; Železný, Filip; Viklický, Ondřej

doi:10.1097/tp.0b013e31824491aa

Cited by 12 publications

(8 citation statements)

References 31 publications

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“…Several studies have identified ATG antibodies with affinities to endovascular adhesion molecules necessary to leukocyte homing and trafficking, which indicates that ATGs may be able to reduce ischemia/reperfusion injury (43,44). In contrast to ATG-F, THG decreased the expression of genes involved in the nuclear factor κB pathway, apoptosis, and chemoattraction even 3 months after the induction (45), which suggests that the effect of THG on inflammation may persist. However, we did not find statistical difference between THG and ATG-F in preventing DGF.…”

Section: Discussionmentioning

confidence: 99%

“…THG and ATG-F have been shown to contain antibodies against several T-cell and B-cell markers, but ATG-F has a lower activity against targeted antigens and a narrower spectrum (5,6), and THG is believed to possess more immune-modulatory and immune-inhibitory potential (45). In a retrospective study involving 342 THG-treated and 142 ATG-F-treated patients with cardiac transplants, the findings corresponded to this speculation clinically: patients who received THG had significantly fewer rejection episodes (8).…”

Section: Discussionmentioning

confidence: 99%

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Thymoglobulin vs. ATG-Fresenius as Induction Therapy in Kidney Transplantation: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Song

Yin²,

Li³

et al. 2020

Front. Immunol.

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Background: Thymoglobulin (THG) and antithymocyte globulin-Fresenius (ATG-F) have not been compared directly as induction therapies in kidney transplantation. Materials and Methods: We performed a Bayesian network meta-analysis to compare THG with ATG-F by pooling direct and indirect evidence. Surface under the cumulative ranking curve (SUCRA) values were used to compare the superiority of one method over the other. Results: A total of 27 randomized controlled trials (RCT) were eligible for the network meta-analysis. Efficacy endpoints, as well as safety indicators, were statistically comparable. For efficacy endpoints, THG seemed inferior to ATG-F in preventing delayed graft function [odds ratio (OR): 1.27; SUCRA: 78% vs. 58%], patient deaths (OR: 2.78; SUCRA: 83% vs. 34%), and graft loss (OR: 1.40; SUCRA: 83% vs. 59%), but superior to ATG-F in biopsy-proven acute rejection (BPAR; OR: 0.59; SUCRA: 78% vs. 39%) and steroid-resistant BPAR prevention (OR: 0.61; SUCRA: 76% vs. 49%) within the first year. For safety endpoints, THG was associated with higher risk of infection (OR: 1.49, SUCRA: 79% vs. 54%), cytomegalovirus infection (OR: 1.04; SUCRA: 40% vs. 37%), de novo diabetes (OR: 1.10; SUCRA: 90% vs. 30%), and malignancy (OR: 8.40; SUCRA: 89% vs. 6%) compared to ATG-F. A subgroup analysis of patients at high risk for immunologic complications revealed similar results, but THG performed better for graft loss (OR: 0.82; SUCRA: 68% vs. 54%). Conclusion: ATG-F seemed to be more effective than THG in improving the short-term kidney transplantation outcomes. Prospective head-to-head comparison of THG and ATG-F with larger sample sizes and longer follow-up is still required.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thymoglobulin vs. ATG-Fresenius as Induction Therapy in Kidney Transplantation: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Song

Yin²,

Li³

et al. 2020

Front. Immunol.

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“… 7 , 56 - 61 A recent report by Urbanova et al. 62 showed that 3 months after induction, thymoglobulin rATG, in contrast to rATG-Fresenius, decreased the expression of genes involved in the nuclear factor-kappa B (NF-κB) pathway (TLR4, MYD88, and CD209), along with CD80 and CTLA4 (costimulation), NLRP1 (apoptosis), CCR10 (chemoattraction), and CLEC4C (dendritic cell function). In an experimental model of kidney reperfusion injury, NF-κB upregulation correlated with the severity of injury, and inhibitors and antagonists of NF-κB had a beneficial effect.…”

Section: Discussionmentioning

confidence: 99%

A Randomized 2×2 Factorial Trial, Part 1

et al. 2015

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“…The entire procedure, ranging from RNA extraction to cDNA synthesis, is in detail described elsewhere [24].…”

Section: Rna Extraction and Cdna Synthesismentioning

confidence: 99%

Molecular Patterns of Subclinical and Clinical Rejection of Kidney Allograft: Quantity Matters

Wohlfahrtová¹,

Tycova²,

Honsová

et al. 2015

Kidney Blood Press Res

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Background/Aims: Subclinical rejection diagnosed from protocol biopsies is thought to be a risk factor of long- term allograft dysfunction. The reason why in some patients subclinical rejection does not represent risk for progression is not fully understood. Methods: The intragraft expression of 376 target genes involved in chemokine defense, apoptosis, inflammation, tolerance and TGF-β signalling pathways was measured using quantitative real-time RT-PCR (2^-∆∆^Ct) method in subclinical inflammation (SCI, n=10), clinical inflammation in acute T-cell mediated rejection (CI, n=10) and no rejection samples (n=9). Results: Clinical inflammation group showed a increased expression of genes for chemotaxis mediating cytokines (CCL1, CCL17, CCL24, CCL25, CCL26), cytokine receptors (CCR1, CCRL2, IL1RAPL2, CXCR5), proinflammatory cytokines (IL12A, LTA), inflammatory mediator (PTAFR), complement protein C3, executioner protein of apoptosis (CASP7), growth factor (TGFA), colony stimulating factor (CSF-2), proteins involved in dendritic cells differentiation and interaction (CD209, LAMP3), regulation of immune response (LILRB2, LILBRB4). The quantitative difference in transcripts signature between SCI and CI is consistent with stronger proinflammatory setting of CI. Prostaglandin E2 receptor gene expression was independently associated with lower risk of further graft function deterioration (OR 0.11, CI 0.01-0.78, p<0.0001). Conclusion: Subclinical acute kidney inflammation has transcriptional profile of immune injury of lower extend compared to clinical acute inflammation.

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Differential Regulation of the Nuclear Factor-κB Pathway by Rabbit Antithymocyte Globulins in Kidney Transplantation

Cited by 12 publications

References 31 publications

Thymoglobulin vs. ATG-Fresenius as Induction Therapy in Kidney Transplantation: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Thymoglobulin vs. ATG-Fresenius as Induction Therapy in Kidney Transplantation: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

A Randomized 2×2 Factorial Trial, Part 1

Molecular Patterns of Subclinical and Clinical Rejection of Kidney Allograft: Quantity Matters

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