Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival

A systematic review and meta-analysis

Antoine Bouquegneau, Charlotte Loheac, Olivier Aubert, Yassine Bouatou, Denis Viglietti, Jean Philippe Empana, Camilo Ulloa, Mohammad Hassan Murad, Christophe Legendre, Denis Glotz, Annette Jackson, Adriana Zeevi, Stephan Schaub, Jean Luc Taupin, Elaine F. Reed, John J. Friedewald, Dolly B. Tyan, Caner Süsal, Ron Shapiro, E. Steve Woodle & 8 others Luis G. Hidalgo, Jacqueline O’Leary, Robert A. Montgomery, Jon Kobashigawa, Xavier Jouven, Patricia Jabre, Carmen Lefaucheur, Alexandre Loupy

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere1002572
JournalPLoS Medicine
Volume15
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Tissue Survival
HLA Antigens
Meta-Analysis
Anti-Idiotypic Antibodies
Tissue Donors
Allografts
Transplants
Antibodies
Clinical Protocols
Biomarkers
Kidney
Organ Transplantation
Observational Studies
Retrospective Studies
Transplantation
Clinical Trials
Databases
Lung
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bouquegneau, A., Loheac, C., Aubert, O., Bouatou, Y., Viglietti, D., Empana, J. P., ... Loupy, A. (2018). Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis. PLoS Medicine, 15(5), [e1002572]. https://doi.org/10.1371/journal.pmed.1002572

Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival : A systematic review and meta-analysis. / Bouquegneau, Antoine; Loheac, Charlotte; Aubert, Olivier; Bouatou, Yassine; Viglietti, Denis; Empana, Jean Philippe; Ulloa, Camilo; Hassan Murad, Mohammad; Legendre, Christophe; Glotz, Denis; Jackson, Annette; Zeevi, Adriana; Schaub, Stephan; Taupin, Jean Luc; Reed, Elaine F.; Friedewald, John J.; Tyan, Dolly B.; Süsal, Caner; Shapiro, Ron; Woodle, E. Steve; Hidalgo, Luis G.; O’Leary, Jacqueline; Montgomery, Robert A.; Kobashigawa, Jon; Jouven, Xavier; Jabre, Patricia; Lefaucheur, Carmen; Loupy, Alexandre.

In: PLoS Medicine, Vol. 15, No. 5, e1002572, 01.05.2018.

Research output: Contribution to journalArticle

Bouquegneau, A, Loheac, C, Aubert, O, Bouatou, Y, Viglietti, D, Empana, JP, Ulloa, C, Hassan Murad, M, Legendre, C, Glotz, D, Jackson, A, Zeevi, A, Schaub, S, Taupin, JL, Reed, EF, Friedewald, JJ, Tyan, DB, Süsal, C, Shapiro, R, Woodle, ES, Hidalgo, LG, O’Leary, J, Montgomery, RA, Kobashigawa, J, Jouven, X, Jabre, P, Lefaucheur, C & Loupy, A 2018, 'Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis', PLoS Medicine, vol. 15, no. 5, e1002572. https://doi.org/10.1371/journal.pmed.1002572
Bouquegneau, Antoine ; Loheac, Charlotte ; Aubert, Olivier ; Bouatou, Yassine ; Viglietti, Denis ; Empana, Jean Philippe ; Ulloa, Camilo ; Hassan Murad, Mohammad ; Legendre, Christophe ; Glotz, Denis ; Jackson, Annette ; Zeevi, Adriana ; Schaub, Stephan ; Taupin, Jean Luc ; Reed, Elaine F. ; Friedewald, John J. ; Tyan, Dolly B. ; Süsal, Caner ; Shapiro, Ron ; Woodle, E. Steve ; Hidalgo, Luis G. ; O’Leary, Jacqueline ; Montgomery, Robert A. ; Kobashigawa, Jon ; Jouven, Xavier ; Jabre, Patricia ; Lefaucheur, Carmen ; Loupy, Alexandre. / Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival : A systematic review and meta-analysis. In: PLoS Medicine. 2018 ; Vol. 15, No. 5.
@article{94cadca0754643f0a6c30c13f41a4f58,
title = "Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis",
abstract = "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.",
author = "Antoine Bouquegneau and Charlotte Loheac and Olivier Aubert and Yassine Bouatou and Denis Viglietti and Empana, {Jean Philippe} and Camilo Ulloa and {Hassan Murad}, Mohammad and Christophe Legendre and Denis Glotz and Annette Jackson and Adriana Zeevi and Stephan Schaub and Taupin, {Jean Luc} and Reed, {Elaine F.} and Friedewald, {John J.} and Tyan, {Dolly B.} and Caner S{\"u}sal and Ron Shapiro and Woodle, {E. Steve} and Hidalgo, {Luis G.} and Jacqueline O’Leary and Montgomery, {Robert A.} and Jon Kobashigawa and Xavier Jouven and Patricia Jabre and Carmen Lefaucheur and Alexandre Loupy",
year = "2018",
month = "5",
day = "1",
doi = "10.1371/journal.pmed.1002572",
language = "English (US)",
volume = "15",
journal = "PLoS Medicine",
issn = "1549-1277",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival

T2 - A systematic review and meta-analysis

AU - Bouquegneau, Antoine

AU - Loheac, Charlotte

AU - Aubert, Olivier

AU - Bouatou, Yassine

AU - Viglietti, Denis

AU - Empana, Jean Philippe

AU - Ulloa, Camilo

AU - Hassan Murad, Mohammad

AU - Legendre, Christophe

AU - Glotz, Denis

AU - Jackson, Annette

AU - Zeevi, Adriana

AU - Schaub, Stephan

AU - Taupin, Jean Luc

AU - Reed, Elaine F.

AU - Friedewald, John J.

AU - Tyan, Dolly B.

AU - Süsal, Caner

AU - Shapiro, Ron

AU - Woodle, E. Steve

AU - Hidalgo, Luis G.

AU - O’Leary, Jacqueline

AU - Montgomery, Robert A.

AU - Kobashigawa, Jon

AU - Jouven, Xavier

AU - Jabre, Patricia

AU - Lefaucheur, Carmen

AU - Loupy, Alexandre

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85047937581&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047937581&partnerID=8YFLogxK

U2 - 10.1371/journal.pmed.1002572

DO - 10.1371/journal.pmed.1002572

M3 - Article

VL - 15

JO - PLoS Medicine

JF - PLoS Medicine

SN - 1549-1277

IS - 5

M1 - e1002572

ER -