The Impact of Interleukin 12B (1188A&gt;C), Interleukin 16 (-295T&gt;C), and Interleukin 18 (607C&gt;A, 137G&gt;C) Gene Polymorphisms on Long-Term Renal Transplant Function and Recipient Outcomes

Pawlus, Jan; Sierocka, Anita; Tejchman, Karol; Ziętek, Z; Romanowski, M; Pawlik, Andrzej; Sieńko, Jerzy; Żukowski, Maciej; Ciechanowski, Kazimierz; Ostrowski, Marek; Sulikowski, Tadeusz

doi:10.1016/j.transproceed.2014.06.019

Cited by 9 publications

(11 citation statements)

References 19 publications

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“…Many studies have investigated the association between cytokine gene polymorphisms and acute renal graft rejection, with different studies reporting different results. [1,3,5,17–25] The variable clinical diagnostic processes, different PRA, HLA match status, immunosuppressive protocols, small sample size, and ethnicity may be the main reasons for the inconsistent results of different studies [26,27]. …”

Section: Discussionmentioning

confidence: 99%

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Xie

Wan

2016

Med Sci Monit

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BackgroundAcute rejection (AR) after renal transplantation affects both patient and graft survival. There is growing evidence of the genetic association between cytokine or its receptor antagonist and AR in solid organ transplantation. The objectives of this study were to investigate the role of recipient TNF β, IL-10, IL-1β, and IL-1 receptor antagonist (ra) gene polymorphism, as well as traditional clinical variables such as panel-reactive antibody (PRA) levels, donor type, and HLA mismatches in AR following renal transplantation.Material/MethodsTNF β (+252A/G), IL-10 (−592A/C), IL-1β (−511C/T) and IL-1ra (86 bp VNTR) gene polymorphisms were determined in 195 renal allograft recipients with and without AR, using PCR. Both these genotypic variants and clinical risk factors were investigated for correlation with AR within the first year after renal transplantation.ResultsPatients with increased pre-transplant PRA levels (P<0.001) and donor type (P=0.012) were prone to the development of AR. After adjusting for all variables of P<0.2, a PRA level >10% (OR=4.515, 95% confidence intervals=1.738–11.727, P=0.002) and the receipt of a graft from a donation after cardiac death (DCD) donor (OR=2.437, 95% confidence intervals=1.047–5.673, P=0.039) remained significantly associated with AR in a multivariate logistic regression analysis. No correlation could be found between recipients with an episode and absence of acute rejection and the gene polymorphisms of these cytokines investigated in the present study.ConclusionsThis study shows that the presence of increased pre-transplant levels of PRA and the receipt of a graft from DCD donor other than cytokine gene polymorphisms are significant risk factors for AR in renal transplantation. To reduce the occurrence of AR, clinicians should take necessary measures to lower the PRA levels and pay more attention to patients who received a graft from a DCD donor.

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Section: Discussionmentioning

confidence: 99%

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Xie

Wan

2016

Med Sci Monit

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“…In addition, IL-18 and NGAL quantiles could accurately predict graft recovery up to three months later [25]. Past studies revealed that IL-18 (rs187238) gene polymorphism was not associated with kidney graft outcome after transplantation [5]. The -137C/G (rs187238) and -607C/A (rs1946518) variant alleles in the IL18 gene were not associated with creatinine clearance, implying that IL-18 polymorphisms could not affect kidney function [26].…”

Section: Role Of Il-18 In Kidney Transplantationmentioning

confidence: 95%

“…In clinic, urinary IL-18 levels were apparently augmented in patients with acute tubular necrosis (ATN) and delayed graft function, therefore, which was suggested as a biomarker for proximal tubular injury in ATN [24]. A significantly increased concentration of IL-18 in urine was observed, which was considered as a biomarker for acute renal failure [5]. IL-18 in combination with NGAL (neutrophil gelatinase-associated lipocalin) was suggested as a biomarker for delayed graft function after kidney transplantation [25].…”

Section: Role Of Il-18 In Kidney Transplantationmentioning

confidence: 99%

“…In addition, IL-18 bearing pleiotropic effects can induce Th2 responses with no need of IL-12 [3]. Boost of Th1 and Th2 immune responses can elicit various cytokines including IL-1␤, IL-2, TNF-␣ (tumor necrosis factor-␣), IFN-␥, adhesion molecules, and apoptosis factors (figure 1) [4][5][6]. IL-18 can be expressed by a wide range of immune cells (T cells, B cells, NK-T cells, neutrophils), although the main source of IL-18 is from the activated macrophages [2].…”

mentioning

confidence: 99%

“…Other non-immune cells can also express IL-18 such as intestinal and airway epithelial cells, keratinocytes, airway epithelium, corneal epithelial cells, renal tubular epithelial cells [7]. The main role of IL-18 is to crucially stimulate lymphocytes to produce the IFN-␥ [5] a equal contribution and regulate macrophages activity, thereby increasing the expression of pro-inflammatory cytokines including IL-6, IL-1␤, CCL4 (macrophage inflammatory protein-1 ␤), CXCL2 (macrophage inflammatory protein-2), and CCL2 (monocyte chemotactic protein-1) [8]. IL-18 in conjunction with IL-12 can stimulate the production of IFN-␥ by B and T cells and potentiate the cytolytic activity of natural killer (NK) cells, and induce Th1 and Th2 responses (figure 1) [9,10].…”

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confidence: 99%

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Role of IL-18 in transplant biology

Liu

Chen

Liu

et al. 2018

European Cytokine Network

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Since pro-inflammatory cytokine IL-18 and its receptor (IL-18R) are closely involved in regulating both adaptive and innate immune responses, it is conceivable that they might play an important role in organ transplantation. IL-18 can stimulate lymphocytes to produce the IFN-␥ and regulate macrophage activity, thereby increasing the expression of proinflammatory cytokines including IL-1␤, IL-6, CCL4 (macrophage inflammatory protein-1 ␤), CXCL2 (macrophage inflammatory protein-2), and CCL2 (monocyte chemotactic protein-1). Nevertheless, the IL-18 signaling pathway and its underlying mechanisms remain obscure in transplant biology. This review is to summarize recent advances in our knowledge about the IL-18 signaling pathway and to analyze their functions in transplant-related biology. It was found that IL-18/IL-18R signaling pathway contributed to vascular transplantation, ischemmia/reperfusion, acute kidney injury, and acute rejection of kidney/liver/heart transplantation. IL-18 was a potential CYP3A expression modulator and was capable of affecting tacrolimus pharmacokinetics. Neutralizing IL-18 by its inhibitor IL-18 binding protein could efficiently suppress the production of injury-associated cytokines such as IL-6, TNF-␣, IFN-␥, CXCL10 (IFN-␥-inducible protein10), and CX 3 CL1 (fractalkine) and improve allograft function. Blockade of IL-18 signaling could regulate cardiomyocyte apoptosis and inhibit Th17 cells differentiation. Alteration of IL-18 levels was suggested as a biomarker for predicting ongoing allograft outcome. All these activities could deepen our understanding of immunobiological role of IL-18 and its receptor in the field of organ transplantation. Intervention of IL-18 signaling pathway might be utilized as a therapeutic strategy in clinic.

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Cytokine Gene Polymorphism Profiles in Kidney Transplant Patients - Association of +1188A/C RS3212227 SNP in the IL12B Gene Prevents Delayed Graft Function

Perović

Marković

Kravljača³

et al. 2018

Archives of Medical Research

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The Impact of Interleukin 12B (1188A>C), Interleukin 16 (-295T>C), and Interleukin 18 (607C>A, 137G>C) Gene Polymorphisms on Long-Term Renal Transplant Function and Recipient Outcomes

Cited by 9 publications

References 19 publications

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Role of IL-18 in transplant biology

Cytokine Gene Polymorphism Profiles in Kidney Transplant Patients - Association of +1188A/C RS3212227 SNP in the IL12B Gene Prevents Delayed Graft Function

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