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MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy

De novo thrombotic microangiopathy (TMA) is associated with poor kidney graft survival, and as we previously described, it is a recipient driven process with suspected genetic background. Direct Sanger sequencing was performed in 90 KTR with de novo TMA and 90 corresponding donors on selected region...

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Autores principales: Petr, Vojtech, Csuka, Dorottya, Hruba, Petra, Szilágyi, Ágnes, Kollar, Marek, Slavcev, Antonij, Prohászka, Zoltán, Viklicky, Ondrej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519137/
https://www.ncbi.nlm.nih.gov/pubmed/36189289
http://dx.doi.org/10.3389/fimmu.2022.985766
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author Petr, Vojtech
Csuka, Dorottya
Hruba, Petra
Szilágyi, Ágnes
Kollar, Marek
Slavcev, Antonij
Prohászka, Zoltán
Viklicky, Ondrej
author_facet Petr, Vojtech
Csuka, Dorottya
Hruba, Petra
Szilágyi, Ágnes
Kollar, Marek
Slavcev, Antonij
Prohászka, Zoltán
Viklicky, Ondrej
author_sort Petr, Vojtech
collection PubMed
description De novo thrombotic microangiopathy (TMA) is associated with poor kidney graft survival, and as we previously described, it is a recipient driven process with suspected genetic background. Direct Sanger sequencing was performed in 90 KTR with de novo TMA and 90 corresponding donors on selected regions in CFH, CD46, C3, and CFB genes that involve variations with a functional effect or confer a risk for aHUS. Additionally, 37 recipients of paired kidneys who did not develop TMA were analyzed for the MCPggaac haplotype. Three-years death-censored graft survival was assessed using Kaplan-Meier and Cox regression models. The distribution of haplotypes in all groups was in the Hardy-Weinberg equilibrium and there was no clustering of haplotypes in any group. In the TMA group, we found that MCPggaac haplotype carriers were at a significantly higher risk of graft loss compared to individuals with the wild-type genotype. Worse 3-year death-censored graft survival was associated with longer cold ischemia time (HR 1.20, 95% CI 1.06, 1.36) and recipients’ MCPggaac haplotype (HR 3.83, 95% CI 1.42, 10.4) in the multivariable Cox regression model. There was no association between donor haplotypes and kidney graft survival. Similarly, there was no effect of the MCPggaac haplotype on 3-year graft survival in recipients of paired kidneys without de novo TMA. Kidney transplant recipients carrying the MCPggaac haplotype with de novo TMA are at an increased risk of premature graft loss. These patients might benefit from therapeutic strategies based on complement inhibition.
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spelling pubmed-95191372022-09-29 MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy Petr, Vojtech Csuka, Dorottya Hruba, Petra Szilágyi, Ágnes Kollar, Marek Slavcev, Antonij Prohászka, Zoltán Viklicky, Ondrej Front Immunol Immunology De novo thrombotic microangiopathy (TMA) is associated with poor kidney graft survival, and as we previously described, it is a recipient driven process with suspected genetic background. Direct Sanger sequencing was performed in 90 KTR with de novo TMA and 90 corresponding donors on selected regions in CFH, CD46, C3, and CFB genes that involve variations with a functional effect or confer a risk for aHUS. Additionally, 37 recipients of paired kidneys who did not develop TMA were analyzed for the MCPggaac haplotype. Three-years death-censored graft survival was assessed using Kaplan-Meier and Cox regression models. The distribution of haplotypes in all groups was in the Hardy-Weinberg equilibrium and there was no clustering of haplotypes in any group. In the TMA group, we found that MCPggaac haplotype carriers were at a significantly higher risk of graft loss compared to individuals with the wild-type genotype. Worse 3-year death-censored graft survival was associated with longer cold ischemia time (HR 1.20, 95% CI 1.06, 1.36) and recipients’ MCPggaac haplotype (HR 3.83, 95% CI 1.42, 10.4) in the multivariable Cox regression model. There was no association between donor haplotypes and kidney graft survival. Similarly, there was no effect of the MCPggaac haplotype on 3-year graft survival in recipients of paired kidneys without de novo TMA. Kidney transplant recipients carrying the MCPggaac haplotype with de novo TMA are at an increased risk of premature graft loss. These patients might benefit from therapeutic strategies based on complement inhibition. Frontiers Media S.A. 2022-09-14 /pmc/articles/PMC9519137/ /pubmed/36189289 http://dx.doi.org/10.3389/fimmu.2022.985766 Text en Copyright © 2022 Petr, Csuka, Hruba, Szilágyi, Kollar, Slavcev, Prohászka and Viklicky https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Petr, Vojtech
Csuka, Dorottya
Hruba, Petra
Szilágyi, Ágnes
Kollar, Marek
Slavcev, Antonij
Prohászka, Zoltán
Viklicky, Ondrej
MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy
title MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy
title_full MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy
title_fullStr MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy
title_full_unstemmed MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy
title_short MCPggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy
title_sort mcpggaac haplotype is associated with poor graft survival in kidney transplant recipients with de novo thrombotic microangiopathy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519137/
https://www.ncbi.nlm.nih.gov/pubmed/36189289
http://dx.doi.org/10.3389/fimmu.2022.985766
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