The role of endothelin II type A receptor (ETAR) in transplant injury

Nowańska, Katarzyna; Grubizna, Krzysztof; Kuriata-Kordek, Magdalena; Krajewska, Magdalena; Banasik, Mirosław

doi:10.1016/j.trim.2021.101505

Cited by 13 publications

(16 citation statements)

References 71 publications

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“…What should be the subject of the upcoming studies is, however, the impact of IDO1 on B cells and the antibody-mediated response, especially when taking donor-specific antibodies into consideration [ 89 ]. Perhaps indoleamine-2,3-dioxygenase will be revealed as a significant factor in this area.…”

Section: Discussionmentioning

confidence: 99%

“…As a matter of fact, antibody-mediated rejection is the leading player in graft immunological injury and transplant loss, with the massive significance of human leukocyte antigen and the anti-HLA and non-HLA antibodies [ 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. Recent studies have shown that especially the non-HLA antibodies, including anti-ETAR antibodies, should be pursued, as their importance is being revealed [ 89 ]. When considering IDO1, some studies [ 90 ] have shown promise in its influence on the humoral response.…”

Section: The Role Of Ido1 In Kidney Allograftsmentioning

confidence: 99%

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Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients

et al. 2022

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Kidney transplantation is unquestionably the most advantageous and preferred treatment when patients with end-stage renal disease are considered. It does have a substantially positive influence on both the quality and expectancy of their lives. Thus, it is quintessential to extend the survival rate of kidney grafts. On account of T-cell-focused treatment, this is being exponentially achieved. The kynurenine pathway, as an immunosuppressive apparatus, and indoleamine 2,3-dioxygenase (IDO1), as its main regulator, are yet to be exhaustively explored. This review presents the recognised role of IDO1 and its influence on the kynurenine pathway, with emphasis on immunosuppression in kidney transplant protection.

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Section: Discussionmentioning

confidence: 99%

Section: The Role Of Ido1 In Kidney Allograftsmentioning

confidence: 99%

Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients

et al. 2022

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“…The complement-independent mechanism is similar to AT1R-Ab, which involves endothelial cell activation and recruitment of inflammatory cells to the graft through ERK signaling pathways, and graft biopsy showed an absence of C4d in immunofluorescence in this scenario. Considering the similarities involved in the vascular lesions, such as endarteritis, fibrinoid necrosis and vascular occlusion secondary to inflammation, vasoconstriction, vascular endothelial and smooth muscle cell proliferation, the histological pattern is probably similar to that determined by AT1R-Ab [ 10 , 23 , 55 ]. Recently, in a basic research study, Catar et al showed that anti-ETAR and AT1R-Ab antibodies could impact microvascular endothelium via β2-arrestin and mTORC2 pathway activation, in a PIK3-dependent and ERK-independent manner [ 56 ].…”

Section: Types Of Non-hla Ab In Kidney Transplantationmentioning

confidence: 78%

“…The phenotype of anti-ETAR antibody mediated graft injury has not been clearly established yet. Two mechanisms through which anti-ETAR antibodies could cause graft injury have been proposed: complement-dependent and independent [ 55 ]. The complement-dependent mechanism involves activation of the classical complement pathway by IgG1-type anti-ETAR antibodies, similar to anti-HLA antibodies, and graft biopsies in these patients show linear C4d fixation in peritubular capillaries on immunofluorescence examination.…”

Section: Types Of Non-hla Ab In Kidney Transplantationmentioning

confidence: 99%

Non-HLA Antibodies in Kidney Transplantation: Immunity and Genetic Insights

et al. 2022

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The polymorphic human leukocyte antigen (HLA) system has been considered the main target for alloimmunity, but the non-HLA antibodies and autoimmunity have gained importance in kidney transplantation (KT). Apart from the endothelial injury, secondary self-antigen exposure and the presence of polymorphic alloantigens, respectively, auto- and allo- non-HLA antibodies shared common steps in their development, such as: antigen recognition via indirect pathway by recipient antigen presenting cells, autoreactive T cell activation, autoreactive B cell activation, T helper 17 cell differentiation, loss of self-tolerance and epitope spreading phenomena. Both alloimmunity and autoimmunity play a synergic role in the formation of non-HLA antibodies, and the emergence of transcriptomics and genome-wide evaluation techniques has led to important progress in understanding the mechanistic features. Among them, non-HLA mismatches between donors and recipients provide valuable information regarding the role of genetics in non-HLA antibody immunity and development.

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“…In our recent studies we described the role of AT1 receptors but also ETA receptors in different renal compartments [32][33][34][35]. The stimulated injury described by authors as vascular changes in microcirculation [23] creates the dangerous opportunity for further damage of the transplant.…”

Section: Discussionmentioning

confidence: 99%

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation

Sikorska

Kamińska

Catar

et al. 2022

JCM

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The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

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The role of endothelin II type A receptor (ETAR) in transplant injury

Cited by 13 publications

References 71 publications

Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients

Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients

Non-HLA Antibodies in Kidney Transplantation: Immunity and Genetic Insights

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation

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