Investigation of association between donors' and recipients' NADPH oxidase p22phox C242T polymorphism and acute rejection, delayed graft function and blood pressure in renal allograft recipients

Mandegary, Ali; Rahmanian-Koshkaki, Sara; Mohammadifar, Mohammad-Amir; Pourgholi, Leyla; Mehdipour, Mohammad; Etminan, Abbas; Ebadzadeh, Mohammad-Reza; Fazeli, Faramarz; Azmandian, Jalal

doi:10.1016/j.trim.2014.08.004

Cited by 7 publications

(8 citation statements)

References 29 publications

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“…In organ transplantation, genetic or environmental factors associated with either the donor or the recipient could influence the rejection of the transplanted organ. For instance, polymorphisms of both the transplant donor [ 37 , 38 ] and recipient [ 39 – 41 ] have been shown to impact graft rejection, and we have previously demonstrated that antibiotic pre-treatment needs to be administered to both the donor and the recipient to result in prolonged skin graft survival [ 20 ]. In the cohousing and fecal transfer experiments described in Figs.…”

Section: Resultsmentioning

confidence: 99%

Gut microbes contribute to variation in solid organ transplant outcomes in mice

McIntosh¹,

Chen²,

Shaiber³

et al. 2018

Microbiome

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BackgroundSolid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics.ResultsWe compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival.ConclusionsThese results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0474-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Gut microbes contribute to variation in solid organ transplant outcomes in mice

McIntosh¹,

Chen²,

Shaiber³

et al. 2018

Microbiome

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“…Another study Mandegary, et al investigated the association between p22 phox (C242T), a polymorphic subunit of NADPH-oxidase, which has a critical role in the activation and stabilization of this prooxidant enzyme involved in the production of superoxide, triggering inflammatory injuries to the kidney. The results showed a significant association between p22 phox C242T polymorphism in the recipient and DGF occurrence [27].…”

Section: Clinical Correlation: Ischaemia-reperfusion Injury and Delayed Graft Functionmentioning

confidence: 81%

Role of ischemia-reperfusion in oxidative stress-mediated injury during kidney transplantation

Ávila¹,

Líbano²,

Rojas³

et al. 2019

Clin Res Trial

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Renal transplant (RT) is the definitive treatment for end-stage renal disease, which is known as a high prevalence pathology with strong economic repercussion both for patients and health systems. Solid organ transplantation is a classically described clinical setting in which massive amounts of reactive oxygen species (ROS) are produced due to ischaemia-reperfusion, thus becoming an essential pathophysiological element involved in delayed graft function in the context of RT. Nevertheless, no clinical protocol yet exists to counteract the damage mediated by ROS intensively produced throughout the transplant process. The available evidence shows a number of successful experiences in the use of antioxidant supplementation and reinforcement over other oxidative stress-related pathologies. This article addresses the pathophysiological role of oxidative stress in RT and its known consequences in function and structure of the allograft, with the objective of gathering consistent information that demonstrates the central role of oxidative stress in this pathology, and to consider it as a possible therapeutic approach in the future.

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“…p22(phox) is a polymorphic subunit of NAD(P)H oxidase that plays a critical role in its activation and stabilization. NAD(P)H oxidase is involved in the production of superoxide that triggers the inflammation in ischaemic kidneys [ 43 , 16 ]. Mandegary et al .…”

Section: Resultsmentioning

confidence: 99%

“…Mandegary et al . [ 16 ] enrolled 196 Iranian donor–recipient pairs to investigate the association between donors’ and recipients’ NADPH oxidase p22(phox) C242T polymorphism and AR, DGF and blood pressure levels in KTRs. Recipient’s p22(phox) 242 T allele (CT + TT) was found to be a major risk factor for DGF, most probably via the overproduction of superoxide at the time of I/R [ 16 ].…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, low-producer polymorphisms have been shown to be deleterious in I/R injury, including rs1695 genotype GG in GSTP1 in KTRs [ 14 ]. Furthermore, high-producer polymorphisms in genes coding for pro-oxidant proteins have been associated with a higher risk of DGF, like NADPH oxidase p22(phox) 242 T allele (CT + TT) in KTRs [ 16 ]. Still, other reports focusing on the oxidative cascade failed to link gene polymorphisms and DGF.…”

Section: Discussionmentioning

confidence: 99%

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Genetic susceptibility to delayed graft function following kidney transplantation: a systematic review of the literature

Huart

Krzesinski

Jouret

2018

Clinical Kidney Journal

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Delayed graft function (DGF) is defined as the need for dialysis within 7 days following kidney transplantation (KTx). DGF is associated with increased costs, higher risk for acute rejection and decreased long-term graft function. Renal ischaemia/reperfusion (I/R) injury plays a major role in DGF occurrence. Single nucleotide polymorphisms (SNPs) in certain genes may aggravate kidney susceptibility to I/R injury, thereby worsening post-transplant outcomes. The present article proposes an extensive review of the literature about the putative impact of donor or recipient SNPs on DGF occurrence in kidney transplant recipients (KTRs). Among 30 relevant PubMed reports, 16 articles identified an association between 18 SNPs and DGF. These polymorphisms concern 14 different well-known genes and one not-yet-identified gene located on chromosome 18. They have been categorized into five groups according to the role of the corresponding proteins in I/R cascade: (i) oxidative stress, (ii) telomere shortening, (iii) chemokines, (iv) T-cell homeostasis and (v) metabolism of anti-inflammatory molecules. The remaining 14 studies failed to demonstrate any association between the studied SNPs and the occurrence of DGF. A better understanding of the genetic susceptibility to renal I/R injury may help prevent DGF and improve clinical outcomes in KTRs.

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Investigation of association between donors' and recipients' NADPH oxidase p22phox C242T polymorphism and acute rejection, delayed graft function and blood pressure in renal allograft recipients

Cited by 7 publications

References 29 publications

Gut microbes contribute to variation in solid organ transplant outcomes in mice

Gut microbes contribute to variation in solid organ transplant outcomes in mice

Role of ischemia-reperfusion in oxidative stress-mediated injury during kidney transplantation

Genetic susceptibility to delayed graft function following kidney transplantation: a systematic review of the literature

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