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De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival

Introduction: De novo anti-HLA donor specific antibodies (DSA) have been inconsistently associated with cardiac allograft vasculopathy (CAV) and long-term mortality. We tested whether C3d-binding de novo DSA were associated with CAV or long-term-survival. Methods: We included 282 consecutive patient...

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Autores principales: Baudry, Guillaume, Pozzi, Matteo, Aubry, Matthieu, Hugon-Vallet, Elisabeth, Mocan, Raluca, Chalabreysse, Lara, Portran, Philippe, Obadia, Jean-François, Thaunat, Olivier, Girerd, Nicolas, Dubois, Valérie, Sebbag, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267850/
https://www.ncbi.nlm.nih.gov/pubmed/35807015
http://dx.doi.org/10.3390/jcm11133731
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author Baudry, Guillaume
Pozzi, Matteo
Aubry, Matthieu
Hugon-Vallet, Elisabeth
Mocan, Raluca
Chalabreysse, Lara
Portran, Philippe
Obadia, Jean-François
Thaunat, Olivier
Girerd, Nicolas
Dubois, Valérie
Sebbag, Laurent
author_facet Baudry, Guillaume
Pozzi, Matteo
Aubry, Matthieu
Hugon-Vallet, Elisabeth
Mocan, Raluca
Chalabreysse, Lara
Portran, Philippe
Obadia, Jean-François
Thaunat, Olivier
Girerd, Nicolas
Dubois, Valérie
Sebbag, Laurent
author_sort Baudry, Guillaume
collection PubMed
description Introduction: De novo anti-HLA donor specific antibodies (DSA) have been inconsistently associated with cardiac allograft vasculopathy (CAV) and long-term mortality. We tested whether C3d-binding de novo DSA were associated with CAV or long-term-survival. Methods: We included 282 consecutive patients without preformed DSA on coronary angiography between 2010 and 2012. Angiographies were classified according to CAV ISHLT grading. The primary outcome was a composite criterion of severe CAV or mortality. As the impact of de novo antibodies should be assessed only after appearance, we used a Cox regression with time-dependent covariables. Results: Of the 282 patients, 51(18%) developed de novo DSA during follow-up, 29 patients had DSA with C3d-binding ability (DSA+C3d+), and 22 were without C3d-binding ability (DSA+C3d-). Compared with patients without DSA, DSA+C3d+ patients had an increased risk for the primary outcome of severe CAV or mortality (adjusted HR = 4.31 (2.40–7.74) p < 0.001) and long-term mortality (adjusted HR = 3.48 (1.97–6.15) p < 0.001) whereas DSA+C3d- did not (adjusted HR = 1.04 (0.43–2.47) p = 0.937 for primary outcome and HR = 1.08 (0.45–2.61) p = 0.866 for mortality). Conclusion: According to this large monocentric study in heart transplant patients, donor specific antibodies were associated with worse clinical outcome when binding complement. DSA and their complement-binding ability should thus be screened for to optimize heart transplant patient follow-up.
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spelling pubmed-92678502022-07-09 De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival Baudry, Guillaume Pozzi, Matteo Aubry, Matthieu Hugon-Vallet, Elisabeth Mocan, Raluca Chalabreysse, Lara Portran, Philippe Obadia, Jean-François Thaunat, Olivier Girerd, Nicolas Dubois, Valérie Sebbag, Laurent J Clin Med Article Introduction: De novo anti-HLA donor specific antibodies (DSA) have been inconsistently associated with cardiac allograft vasculopathy (CAV) and long-term mortality. We tested whether C3d-binding de novo DSA were associated with CAV or long-term-survival. Methods: We included 282 consecutive patients without preformed DSA on coronary angiography between 2010 and 2012. Angiographies were classified according to CAV ISHLT grading. The primary outcome was a composite criterion of severe CAV or mortality. As the impact of de novo antibodies should be assessed only after appearance, we used a Cox regression with time-dependent covariables. Results: Of the 282 patients, 51(18%) developed de novo DSA during follow-up, 29 patients had DSA with C3d-binding ability (DSA+C3d+), and 22 were without C3d-binding ability (DSA+C3d-). Compared with patients without DSA, DSA+C3d+ patients had an increased risk for the primary outcome of severe CAV or mortality (adjusted HR = 4.31 (2.40–7.74) p < 0.001) and long-term mortality (adjusted HR = 3.48 (1.97–6.15) p < 0.001) whereas DSA+C3d- did not (adjusted HR = 1.04 (0.43–2.47) p = 0.937 for primary outcome and HR = 1.08 (0.45–2.61) p = 0.866 for mortality). Conclusion: According to this large monocentric study in heart transplant patients, donor specific antibodies were associated with worse clinical outcome when binding complement. DSA and their complement-binding ability should thus be screened for to optimize heart transplant patient follow-up. MDPI 2022-06-28 /pmc/articles/PMC9267850/ /pubmed/35807015 http://dx.doi.org/10.3390/jcm11133731 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Baudry, Guillaume
Pozzi, Matteo
Aubry, Matthieu
Hugon-Vallet, Elisabeth
Mocan, Raluca
Chalabreysse, Lara
Portran, Philippe
Obadia, Jean-François
Thaunat, Olivier
Girerd, Nicolas
Dubois, Valérie
Sebbag, Laurent
De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival
title De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival
title_full De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival
title_fullStr De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival
title_full_unstemmed De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival
title_short De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival
title_sort de novo complement-binding anti-hla antibodies in heart transplanted patients is associated with severe cardiac allograft vasculopathy and poor long-term survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267850/
https://www.ncbi.nlm.nih.gov/pubmed/35807015
http://dx.doi.org/10.3390/jcm11133731
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