Elevated intragraft expression of innate immunity and cell death-related markers is a risk factor for adverse graft outcome

Yang, Jianxin; Snijders, Malou L H; Haasnoot, Geert W.; Kooten, Cees van; Mallat, M.; Fijter, Johan W. de; Groningen, Marian C. Clahsen-van; Claas, Frans H.J.; Eikmans, Michael

doi:10.1016/j.trim.2018.02.009

Cited by 5 publications

(6 citation statements)

References 45 publications

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“…Additionally, the majority of predictive transcriptomic studies in KT have focused on DGF as a surrogate marker, without being able to predict longer-term outcomes (>12 months). 27,28,[30][31][32][33][34][35] We found that DGF was not significantly associated with 24-month function (p = .238), explaining why gene sets associated with DGF have poor predictive value. 8,36 Furthermore, most transcriptomic studies have utilized postreperfusion biopsies, which are less likely to capture intrinsic organ quality due to the "transcriptional noise" induced by reperfusion injury, surgical procedures, recipient immune infiltration, and immunosuppressive medications.…”

Section: Discussionmentioning

confidence: 70%

“…Thus far, a limited number of peer-reviewed pretransplant kidney GE studies have been conducted in the field. [25][26][27][28][29][30][31][32][33] Of these studies, only two evaluated graft outcomes beyond 1 year (both of which had small sample sizes and used targeted gene approaches). 29,33 Critically, none of the previous studies included external validations, which are necessary to determine the reproducibility and generalizability of results in different patient populations.…”

Section: Discussionmentioning

confidence: 99%

“…Thus far, a limited number of peer‐reviewed pretransplant kidney GE studies have been conducted in the field 25–33 . Of these studies, only two evaluated graft outcomes beyond 1 year (both of which had small sample sizes and used targeted gene approaches) 29,33 .…”

Section: Discussionmentioning

confidence: 99%

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Pretransplant kidney transcriptome captures intrinsic donor organ quality and predicts 24-month outcomes

Archer

Bardhi

Maluf

et al. 2022

American Journal of Transplantation

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Pretransplant kidney transcriptome captures intrinsic donor organ quality and predicts 24-month outcomes

Archer

Bardhi

Maluf

et al. 2022

American Journal of Transplantation

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“…BCL2 (BCL2 Apoptosis Regulator) is an anti-apoptotic protein that prevents the death of specific cells like lymphocytes. The expression of BCL2 may reflect the enhancement of cell death and immunogenicity risk signals in transplantation and constitute a risk factor for poor transplantation results ( 31 ). Further, HSPA4 is expressed in heat resistance, damage signaling molecules (DAMPs), and ICD ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

An immunogenic cell death-related regulators classification patterns and immune microenvironment infiltration characterization in intracranial aneurysm based on machine learning

et al. 2022

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BackgroundImmunogenic Cell Death (ICD) is a novel way to regulate cell death and can sufficiently activate adaptive immune responses. Its role in immunity is still emerging. However, the involvement of ICD in Intracranial Aneurysms (IA) remains unclear. This study aimed to identify biomarkers associated with ICDs and determine the relationship between them and the immune microenvironment during the onset and progression of IAMethodsThe IA gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IA were identified and the effects of the ICD on immune microenvironment signatures were studied. Techniques like Lasso, Bayes, DT, FDA, GBM, NNET, RG, SVM, LR, and multivariate analysis were used to identify the ICD gene signatures in IA. A consensus clustering algorithm was used for conducting the unsupervised cluster analysis of the ICD patterns in IA. Furthermore, enrichment analysis was carried out for investigating the various immune responses and other functional pathways. Along with functional annotation, the weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network and module construction, identification of the hub gene, and co-expression analysis were also carried out.ResultsThe above techniques were used for establishing the ICD gene signatures of HMGB1, HMGN1, IL33, BCL2, HSPA4, PANX1, TLR9, CLEC7A, and NLRP3 that could easily distinguish IA from normal samples. The unsupervised cluster analysis helped in identifying three ICD gene patterns in different datasets. Gene enrichment analysis revealed that the IA samples showed many differences in pathways such as the cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, chemokine signaling pathway, NOD-like receptor signaling pathway, viral protein interaction with the cytokines and cytokine receptors, and a few other signaling pathways compared to normal samples. In addition, the three ICD modification modes showed obvious differences in their immune microenvironment and the biological function pathways. Eight ICD-regulators were identified and showed meaningful associations with IA, suggesting they could severe as potential prognostic biomarkers.ConclusionsA new gene signature for IA based on ICD features was created. This signature shows that the ICD pattern and the immune microenvironment are closely related to IA and provide a basis for optimizing risk monitoring, clinical decision-making, and developing novel treatment strategies for patients with IA.

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“…Another possible reason is that AKI can induce the activation of innate immune system. After transplant, it can be a crosstalk to the activation of allograft rejection [28][29][30] . Taken together, the main reason of the adverse allograft outcome in AKI-elderly-DDKT subgroup might be the low nephron mass at baseline.…”

Section: Discussionmentioning

confidence: 99%

Impact of acute kidney injury in elderly versus young deceased donors on post-transplant outcomes: A multicenter cohort study

Park

Kim

et al. 2020

Sci Rep

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We investigated the impact of acute kidney injury (AKi) in elderly deceased-donors (DDs) vs. AKi in young DDs on post-transplant clinical outcomes. A total of 709 kidney transplant recipients (KTRs) from 602 DDs at four transplant centers were enrolled. KTRs were divided into young-DDKT and elderly-DDKT groups according to the age of DD of 60 years. Both groups were subdivided into non-AKI-KT and AKI-KT subgroups according to AKI in DDs. We investigated short-term and long-term clinical outcomes of non-AKI-DDKT and AKI-DDKT subgroups within young-DDKT and elderly-DDKT groups. The incidence of DGF in the AKI-DDKT subgroup was higher and the allograft function within 12 months after KT in the AKI-DDKT subgroup was lower than those in the non-AKI-DDKT subgroup in both young-DDKT and elderly-DDKT groups. Death-censored allograft survival rate was significantly lower in the AKI-elderly-DDKT subgroup than that in the non-AKI-elderly-DDKT subgroup, but it did not differ between AKI-young-DDKT and non-AKI-young-DDKT subgroup. In multivariable analysis, AKI-elderly-DDKT was an independent risk factor for allograft failure (hazard ratio: 2.648, 95% CI: 1.170-5.994, p = 0.019) and a significant interaction between AKI and old age in DDs on allograft failure was observed (p = 0.001). AKI in elderly DDs, but not in young DDs, can significantly affect long-term allograft outcomes of KtRs. With a tremendous increase in the number of patients with end-stage renal disease, donor shortage in kidney transplantation (KT) has become a worldwide crucial issue to solve 1-3. In this regard, the use of kidneys from elderly deceased donors (DDs) has been proposed as an important strategy for solving this donor shortage 4-7. It has been reported that the proportion of elderly brain death patients was higher than that of younger brain death patients and that KT from elderly DDs could give survival benefit in comparison with those remaining on dialysis 8. In addition, in contrast to living donor KT, kidney donation from elderly DD is fully free from donor safety issue. These reasons justify the use of kidney from elderly DDs.

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Elevated intragraft expression of innate immunity and cell death-related markers is a risk factor for adverse graft outcome

Abstract: Complement- and apoptosis-related gene expression is elevated in deceased donor transplants before transplantation. High BAX:BCL2 ratio and TLR4 expression during AR may reflect enhanced intragraft cell death and immunogenic danger signals, and pose a risk factor for adverse graft outcome.

Cited by 5 publications

References 45 publications

Pretransplant kidney transcriptome captures intrinsic donor organ quality and predicts 24-month outcomes

Pretransplant kidney transcriptome captures intrinsic donor organ quality and predicts 24-month outcomes

An immunogenic cell death-related regulators classification patterns and immune microenvironment infiltration characterization in intracranial aneurysm based on machine learning

Impact of acute kidney injury in elderly versus young deceased donors on post-transplant outcomes: A multicenter cohort study

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