<i>TLR9</i> gene polymorphism (rs187084, rs352140): association with acute rejection and estimated glomerular filtration rate in renal transplant recipients

Kim, T. H.; Jeong, Kyung-Hwan; Kim, S. K.; Lee, S. H.; Ihm, Chun-Gyoo; Lee, T. W.; Moon, Jae‐Young; Yoon, Young Chul; Chung, Joo‐Ho; Park, S. J.; Kang, Sun Woo; Kim, Y. H.

doi:10.1111/iji.12069

Cited by 13 publications

(10 citation statements)

References 29 publications

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“…Mature MDCs support T helper type 1 development. 40 The triggering mechanism is multifactorial. One of the proposed theories considers the delayed effects of IRI-dependent cellular stress, which induces the production of C3a (and C5a) and the release of DAMPs within the donor's organ.…”

Section: Acute Kidney Injurymentioning

confidence: 99%

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Zmonarski¹,

Banasik²,

Madziarska³

et al. 2019

Adv Clin Exp Med

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Krajewska M. The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells. AbstractThe innate immune system is activated before an adaptive immune response. An expression of a particular toll-like receptor (TLR) in a transplanted kidney depends on the localization of specific cells (e.g., endothelium, elements of the nephron structure), recent pathology and the time passed since transplantation. The TLR4 receptor is expressed on renal tubular epithelial (RTE) and endothelial cells, podocytes, blood and interstitial monocytes/macrophages, and dendritic cells. While circulating in blood, some monocytes are attracted and penetrate the transplanted organ, where they supplement the donor's resident macrophages. The intensity of migration depends on the local activation of inflammation in the graft and on the expression of specific receptors on kidney endothelial cells and monocytes/macrophages. The percentage of cells with shifted TLR4 expression usually increases in circulating monocytes. The TLR4 and the biochemical stimulation cascade derived from it in any type of cell, including monocytes, undergo multi-level regulation with feedback loops with other components of the primary system, and are also dependent on the action of immunosuppression. Toll-like receptor 4 senses stimuli that make monocytes contribute differently both to acute/chronic kidney injuries and to the development of tolerance. After kidney transplantation, TLR4 expression and related cytokine production capacity may vary depending on past diseases and oncoming problems. Since conventional immunosuppression does not prevent chronic allograft injury (CAI), peripheral blood monocytes and TLR4 constitute candidates for diagnostic and therapeutic targets. Considering the mutual communication among various elements of the primary immune system, future therapeutic intervention should be directed toward factors directly or indirectly regulating the expression or post-receptor signaling of the TLR4 receptor.

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Section: Acute Kidney Injurymentioning

confidence: 99%

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Zmonarski¹,

Banasik²,

Madziarska³

et al. 2019

Adv Clin Exp Med

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“…The role of TLR9 SNPs is still unclear, but it was demonstrated that TLR9 T-1486C promoter polymorphism modifies the expression and, consequently, its function (24). This polymorphism has been investigated in different diseases, and it has been recognized that this mutation increases the risk of asthma (24), has a significant association with Crohn's disease (25) and with the risk of acute rejection in renal transplants (26), but it is not linked with susceptibility to systemic lupus erythematosus (15). Circulating bacterial-derived DNA fragments commonly exist in the blood of ESRD patients under HD.…”

Section: Discussionmentioning

confidence: 99%

TLR4 and TLR9 Polymorphisms Effect on Inflammatory Response in End-Stage Renal Disease Patients

et al. 2014

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Toll-like receptors (TLRs) playa key role in the response of innate and adaptive immune system to microbial and endogenous ligands. Inflammation is a common feature in end-stage renal disease (ESRD) patients; however, the mechanisms/factors triggering the inflammatory process are still poorly clarified. Our aim was to analyze the impact of the c.-1486T>C and c.896A>G polymorphisms in TLR9 and TLR4 genes, respectively, on the inflammatory response of ESRD patients. Clinical and laboratory evaluation was carried out on 184 ESRD patients. Polymerase chain reaction followed by restriction fragmens length polymorphisms (PCR-RFLP) was employed for genotyping of TLR-4 c.896A>G and TLR-9 c.-1486T>C polymorphisms. The prevalence of AA and AG of TLR4 c.896A>G polymorphism in ESRD patients was 97.8% and 2.2%, respectively. None of the individuals showed a homozygous TLR4 polymorphism. Concerning the TLR9 c.-1486T>C polymorphism, we found that ESRD patients showed a prevalence of TC and CC genotypes of 57.1% and 20.6%, respectively. We found that the heterozygous patients for the TLR4 c.896A>G polymorphism presented an increased level in lymphocyte count, a decrease in neutrophil/lymphocyte ratio and in serum levels of hepcidin. Regarding the TLR9 c.-1486T>C polymorphism, we found that it is associated with decreased white blood cell and neutrophil counts, ferritin and CRP serum levels, and with an increase in serum levels of creatinine. Our data suggest that the presence of the studied polymorphisms is associated with a decreased inflammatory response in ESRD patients under hemodialysis, and, thus its presence might have beneficial effects in ESRD patients. Moreover, our data provide new insights in the role of TLR polymorphisms in renal disease, which might have impact in the near future for the development of innovative therapies.

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“…A similar study involving Toll-like receptor 9 (TLR-9) investigated the relationship between TLR-9 polymorphisms and kidney allograft outcomes. Two TLR-9 gene SNPs, rs187084 and rs352140, contributed to the susceptibility for acute rejection in renal transplants (P = 0.013 and P = 0.019, respectively) [ 34 ].…”

Section: Biomarkersmentioning

confidence: 99%

An Insight Into the Immunologic Events and Risk Assessment in Renal Transplantation

et al. 2016

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Organ transplantation has always been considered to be the optimal therapeutic intervention in patients with end-stage organ failure. In the US, approximately 615,000 patients are diagnosed with end-stage renal disease and less than 30% have received a kidney transplant. One of the crucial drawbacks in successful renal transplantation is allograft rejection. Survival rates among transplant recipients have greatly improved due to better understanding of transplant biology and more effective immunosuppressive agents. Post-transplant immune monitoring and optimization of the immunosuppressive therapy using non-invasive biomarkers can effectively predict impending graft rejection and may spare the need for renal biopsy. This article provides an insight into the immunomodulations of renal transplant recipients. It depicts the immune system including several types of kidney rejection and reviews the biomarkers that may serve in near future, as surveillance tools for graft monitoring. Finally, a summary on the main immunosuppressive drugs used in kidney transplant both in the induction and maintenance phases is also covered.

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TLR9 gene polymorphism (rs187084, rs352140): association with acute rejection and estimated glomerular filtration rate in renal transplant recipients

Cited by 13 publications

References 29 publications

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

TLR4 and TLR9 Polymorphisms Effect on Inflammatory Response in End-Stage Renal Disease Patients

An Insight Into the Immunologic Events and Risk Assessment in Renal Transplantation

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