Article (Scientific journals)
Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis
BOUQUEGNEAU, Antoine; Loheac, C.; Aubert, O. et al.
2018In PLoS Medicine, 15 (5)
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Keywords :
HLA antibody; HLA antigen; Article; Antibodies; Complement Activation; Graft Rejection; Graft Survival; HLA Antigens; Humans; Transplantation Immunology
Abstract :
[en] Background: Anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are recognized as a major barrier to patients’ access to organ transplantation and the major cause of graft failure. The capacity of circulating anti-HLA DSAs to activate complement has been suggested as a potential biomarker for optimizing graft allocation and improving the rate of successful transplantations. Methods and findings: To address the clinical relevance of complement-activating anti-HLA DSAs across all solid organ transplant patients, we performed a meta-analysis of their association with transplant outcome through a systematic review, from inception to January 31, 2018. The primary outcome was allograft loss, and the secondary outcome was allograft rejection. A comprehensive search strategy was conducted through several databases (Medline, Embase, Cochrane, and Scopus). A total of 5,861 eligible citations were identified. A total of 37 studies were included in the meta-analysis. Studies reported on 7,936 patients, including kidney (n = 5,991), liver (n = 1,459), heart (n = 370), and lung recipients (n = 116). Solid organ transplant recipients with circulating complement-activating anti-HLA DSAs experienced an increased risk of allograft loss (pooled HR 3.09; 95% CI 2.55–3.74, P = 0.001; I2= 29.3%), and allograft rejection (pooled HR 3.75; 95% CI: 2.05–6.87, P = 0.001; I2= 69.8%) compared to patients without complement-activating anti-HLA DSAs. The association between circulating complement-activating anti-HLA DSAs and allograft failure was consistent across all subgroups and sensitivity analyses. Limitations of the study are the observational and retrospective design of almost all included studies, the higher proportion of kidney recipients compared to other solid organ transplant recipients, and the inclusion of fewer studies investigating allograft rejection. Conclusions: In this study, we found that circulating complement-activating anti-HLA DSAs had a significant deleterious impact on solid organ transplant survival and risk of rejection. The detection of complement-activating anti-HLA DSAs may add value at an individual patient level for noninvasive biomarker-guided risk stratification. Trial registration: National Clinical Trial protocol ID: NCT03438058. © 2018 Bouquegneau et al. http://creativecommons.org/licenses/by/4.0/
Disciplines :
Urology & nephrology
Author, co-author :
BOUQUEGNEAU, Antoine  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie
Loheac, C.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France
Aubert, O.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, Department of Kidney Transplantation, Necker Hospital, Paris Descartes University and Assistance Publique–Hôpitaux de Paris (AP–HP), Paris, France
Bouatou, Y.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, Division of Nephrology, Geneva University Hospitals, Geneva, Switzerland
Viglietti, D.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, Department of Nephrology and Kidney Transplantation, Saint–Louis Hospital, Paris Diderot University, AP–HP, Paris, France
Empana, J. P.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France
Ulloa, C.;  Hospital Barros Luco Trudeau, Santiago et Clinica Alemana de Santiago, Chile
Hassan Murad, M.;  Mayo Clinic Evidence–based Practice Center, Mayo Clinic, Rochester, MN, United States
Legendre, C.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, Department of Kidney Transplantation, Necker Hospital, Paris Descartes University and Assistance Publique–Hôpitaux de Paris (AP–HP), Paris, France
Glotz, D.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, Department of Nephrology and Kidney Transplantation, Saint–Louis Hospital, Paris Diderot University, AP–HP, Paris, France
Jackson, A. M.;  Immunogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Zeevi, A.;  Department of Pathology, Surgery and Immunology at University of Pittsburgh Medical Center, Pittsburgh, PA, United States
Schaub, S.;  Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
Taupin, J. L.;  Department of Immunology and Histocompatibility, CHU Paris–GH St–Louis Lariboisière, Paris, France
Reed, E. F.;  Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, David Geffen School of Medicine, University of California, Los Angeles, CA, United States
Friedewald, J. J.;  Northwestern University Feinberg School of Medicine, Comprehensive Transplant Center, Division of Transplant Surgery, Chicago, IL, United States
Tyan, D. B.;  Division of Nephrology, Department of Medicine, Stanford University, Stanford, CA, United States
Süsal, C.;  Institute of Immunology, Heidelberg University, Department of Transplantation Immunology, Heidelberg, Germany
Shapiro, R.;  Kidney/Pancreas Transplant Program, Mount Sinai Hospital, Recanati Miller Transplantation Institute, New York, NY, United States
Woodle, E. S.;  Division of Transplantation, Department of Surgery and Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
Hidalgo, L. G.;  Department of Laboratory Medicine and Pathology and Alberta Transplant Applied Genomics Center, Edmonton, AB, Canada
O’Leary, J.;  Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
Montgomery, R. A.;  The NYU Transplant Institute, New York University Langone Medical Center, New York, NY, United States
Kobashigawa, J.;  Cedars–Sinai Heart Institute, Los Angeles, CA, United States
Jouven, X.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, Department of Cardiology and Global Health Unit European Georges Pompidou Hospital, Paris, France
Jabre, P.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, SAMU of Paris, Necker Hospital, Paris, France, Paris Descartes University, Paris, France, AP–HP, Paris, France
Lefaucheur, C.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, Department of Nephrology and Kidney Transplantation, Saint–Louis Hospital, Paris Diderot University, AP–HP, Paris, France
Loupy, A.;  Paris Translational Research Center for Organ Transplantation INSERM Unit 970, Paris, France, Department of Kidney Transplantation, Necker Hospital, Paris Descartes University and Assistance Publique–Hôpitaux de Paris (AP–HP), Paris, France
More authors (18 more) Less
Language :
English
Title :
Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis
Publication date :
2018
Journal title :
PLoS Medicine
ISSN :
1549-1277
eISSN :
1549-1676
Publisher :
Public Library of Science
Volume :
15
Issue :
5
Peer reviewed :
Peer Reviewed verified by ORBi
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