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The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study
BACKGROUND: Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antig...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532952/ https://www.ncbi.nlm.nih.gov/pubmed/36211367 http://dx.doi.org/10.3389/fimmu.2022.1005790 |
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author | Frischknecht, Lukas Deng, Yun Wehmeier, Caroline de Rougemont, Olivier Villard, Jean Ferrari-Lacraz, Sylvie Golshayan, Déla Gannagé, Monique Binet, Isabelle Wirthmueller, Urs Sidler, Daniel Schachtner, Thomas Schaub, Stefan Nilsson, Jakob |
author_facet | Frischknecht, Lukas Deng, Yun Wehmeier, Caroline de Rougemont, Olivier Villard, Jean Ferrari-Lacraz, Sylvie Golshayan, Déla Gannagé, Monique Binet, Isabelle Wirthmueller, Urs Sidler, Daniel Schachtner, Thomas Schaub, Stefan Nilsson, Jakob |
author_sort | Frischknecht, Lukas |
collection | PubMed |
description | BACKGROUND: Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM). METHODS: We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls. RESULTS: Pre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR. CONCLUSION: Our results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA. |
format | Online Article Text |
id | pubmed-9532952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95329522022-10-06 The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study Frischknecht, Lukas Deng, Yun Wehmeier, Caroline de Rougemont, Olivier Villard, Jean Ferrari-Lacraz, Sylvie Golshayan, Déla Gannagé, Monique Binet, Isabelle Wirthmueller, Urs Sidler, Daniel Schachtner, Thomas Schaub, Stefan Nilsson, Jakob Front Immunol Immunology BACKGROUND: Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM). METHODS: We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls. RESULTS: Pre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR. CONCLUSION: Our results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA. Frontiers Media S.A. 2022-09-21 /pmc/articles/PMC9532952/ /pubmed/36211367 http://dx.doi.org/10.3389/fimmu.2022.1005790 Text en Copyright © 2022 Frischknecht, Deng, Wehmeier, de Rougemont, Villard, Ferrari-Lacraz, Golshayan, Gannagé, Binet, Wirthmueller, Sidler, Schachtner, Schaub, Nilsson and the Swiss Transplant Cohort Study 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 Frischknecht, Lukas Deng, Yun Wehmeier, Caroline de Rougemont, Olivier Villard, Jean Ferrari-Lacraz, Sylvie Golshayan, Déla Gannagé, Monique Binet, Isabelle Wirthmueller, Urs Sidler, Daniel Schachtner, Thomas Schaub, Stefan Nilsson, Jakob The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study |
title | The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study |
title_full | The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study |
title_fullStr | The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study |
title_full_unstemmed | The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study |
title_short | The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study |
title_sort | impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – data from the swiss transplant cohort study |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532952/ https://www.ncbi.nlm.nih.gov/pubmed/36211367 http://dx.doi.org/10.3389/fimmu.2022.1005790 |
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