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Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal

INTRODUCTION: Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complemen...

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Autores principales: Al-Awadhi, Solaf, Raynaud, Marc, Louis, Kevin, Bouquegneau, Antoine, Taupin, Jean-Luc, Aubert, Olivier, Loupy, Alexandre, Lefaucheur, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577173/
https://www.ncbi.nlm.nih.gov/pubmed/37849755
http://dx.doi.org/10.3389/fimmu.2023.1265796
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author Al-Awadhi, Solaf
Raynaud, Marc
Louis, Kevin
Bouquegneau, Antoine
Taupin, Jean-Luc
Aubert, Olivier
Loupy, Alexandre
Lefaucheur, Carmen
author_facet Al-Awadhi, Solaf
Raynaud, Marc
Louis, Kevin
Bouquegneau, Antoine
Taupin, Jean-Luc
Aubert, Olivier
Loupy, Alexandre
Lefaucheur, Carmen
author_sort Al-Awadhi, Solaf
collection PubMed
description INTRODUCTION: Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking. METHODS: We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level. RESULTS: In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss. DISCUSSION: We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
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spelling pubmed-105771732023-10-17 Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal Al-Awadhi, Solaf Raynaud, Marc Louis, Kevin Bouquegneau, Antoine Taupin, Jean-Luc Aubert, Olivier Loupy, Alexandre Lefaucheur, Carmen Front Immunol Immunology INTRODUCTION: Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking. METHODS: We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level. RESULTS: In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss. DISCUSSION: We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection. Frontiers Media S.A. 2023-10-02 /pmc/articles/PMC10577173/ /pubmed/37849755 http://dx.doi.org/10.3389/fimmu.2023.1265796 Text en Copyright © 2023 Al-Awadhi, Raynaud, Louis, Bouquegneau, Taupin, Aubert, Loupy and Lefaucheur 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
Al-Awadhi, Solaf
Raynaud, Marc
Louis, Kevin
Bouquegneau, Antoine
Taupin, Jean-Luc
Aubert, Olivier
Loupy, Alexandre
Lefaucheur, Carmen
Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
title Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
title_full Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
title_fullStr Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
title_full_unstemmed Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
title_short Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
title_sort complement-activating donor-specific anti-hla antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577173/
https://www.ncbi.nlm.nih.gov/pubmed/37849755
http://dx.doi.org/10.3389/fimmu.2023.1265796
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