anti-HLA; complement-activation; donor specific antibodies; rejection; transplantation outcomes; Complement System Proteins; HLA Antigens; Humans; Transplantation, Homologous; Graft Rejection; Organ Transplantation/adverse effects; Organ Transplantation; Immunology and Allergy; Immunology
Abstract :
[en] [en] 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.
Disciplines :
General & internal medicine
Author, co-author :
Al-Awadhi, Solaf; Université de Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S970, Paris Cardiovascular Research Center (PARCC), Paris Translational Research Centre for Organ Transplantation, Paris, France
Raynaud, Marc; Université de Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S970, Paris Cardiovascular Research Center (PARCC), Paris Translational Research Centre for Organ Transplantation, Paris, France
Louis, Kevin; Université de Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S970, Paris Cardiovascular Research Center (PARCC), Paris Translational Research Centre for Organ Transplantation, Paris, France ; Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
Bouquegneau, Antoine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de néphrologie ; Université de Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S970, Paris Cardiovascular Research Center (PARCC), Paris Translational Research Centre for Organ Transplantation, Paris, France
Taupin, Jean-Luc; Department of Immunology and Histocompatibility, Centre Hospitalier Universitaire (CHU) Paris-GH St-Louis Lariboisière, Paris, France
Aubert, Olivier; Université de Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S970, Paris Cardiovascular Research Center (PARCC), Paris Translational Research Centre for Organ Transplantation, Paris, France ; Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
Loupy, Alexandre; Université de Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S970, Paris Cardiovascular Research Center (PARCC), Paris Translational Research Centre for Organ Transplantation, Paris, France ; Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
Lefaucheur, Carmen; Université de Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)-S970, Paris Cardiovascular Research Center (PARCC), Paris Translational Research Centre for Organ Transplantation, Paris, France ; Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
Language :
English
Title :
Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal.
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