C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection
C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9—indicative of complement-mediated injury—is a...
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Frontiers Media S.A.
2019-03-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00235/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valentin Goutaudier Hélène Perrochia Simon Mucha Marie Bonnet Sylvie Delmas Florian Garo Valérie Garrigue Sébastien Lepreux Vincent Pernin Vincent Pernin Jean-Emmanuel Serre Ilan Szwarc Pierre Merville Pierre Merville Annie Ramounau-Pigot Céline René Jonathan Visentin Jonathan Visentin Bryan Paul Morgan Véronique Frémeaux-Bacchi Georges Mourad Lionel Couzi Lionel Couzi Moglie Le Quintrec Moglie Le Quintrec |
spellingShingle |
Valentin Goutaudier Hélène Perrochia Simon Mucha Marie Bonnet Sylvie Delmas Florian Garo Valérie Garrigue Sébastien Lepreux Vincent Pernin Vincent Pernin Jean-Emmanuel Serre Ilan Szwarc Pierre Merville Pierre Merville Annie Ramounau-Pigot Céline René Jonathan Visentin Jonathan Visentin Bryan Paul Morgan Véronique Frémeaux-Bacchi Georges Mourad Lionel Couzi Lionel Couzi Moglie Le Quintrec Moglie Le Quintrec C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection Frontiers in Immunology antibody-mediated rejection kidney transplantation complement C4d C5b9 |
author_facet |
Valentin Goutaudier Hélène Perrochia Simon Mucha Marie Bonnet Sylvie Delmas Florian Garo Valérie Garrigue Sébastien Lepreux Vincent Pernin Vincent Pernin Jean-Emmanuel Serre Ilan Szwarc Pierre Merville Pierre Merville Annie Ramounau-Pigot Céline René Jonathan Visentin Jonathan Visentin Bryan Paul Morgan Véronique Frémeaux-Bacchi Georges Mourad Lionel Couzi Lionel Couzi Moglie Le Quintrec Moglie Le Quintrec |
author_sort |
Valentin Goutaudier |
title |
C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection |
title_short |
C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection |
title_full |
C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection |
title_fullStr |
C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection |
title_full_unstemmed |
C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection |
title_sort |
c5b9 deposition in glomerular capillaries is associated with poor kidney allograft survival in antibody-mediated rejection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-03-01 |
description |
C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9—indicative of complement-mediated injury—is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25–73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9– ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients. |
topic |
antibody-mediated rejection kidney transplantation complement C4d C5b9 |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00235/full |
work_keys_str_mv |
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doaj-e1aa5ae304a943a59be7b7d2653913002020-11-24T21:29:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00235437246C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated RejectionValentin Goutaudier0Hélène Perrochia1Simon Mucha2Marie Bonnet3Sylvie Delmas4Florian Garo5Valérie Garrigue6Sébastien Lepreux7Vincent Pernin8Vincent Pernin9Jean-Emmanuel Serre10Ilan Szwarc11Pierre Merville12Pierre Merville13Annie Ramounau-Pigot14Céline René15Jonathan Visentin16Jonathan Visentin17Bryan Paul Morgan18Véronique Frémeaux-Bacchi19Georges Mourad20Lionel Couzi21Lionel Couzi22Moglie Le Quintrec23Moglie Le Quintrec24University of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceDepartment of Pathology, Gui de Chauliac Hospital, Montpellier University Hospital, Montpellier, FranceDepartment of Nephrology, Transplantation, Dialysis and Apheresis, Pellegrin Hospital, Bordeaux University Hospital, Bordeaux, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceDepartment of Pathology, Pellegrin Hospital, Bordeaux University Hospital, Bordeaux, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceINSERM U1183, Institute for Regenerative Medicine and Biotherapy, Saint-Eloi Hospital, Montpellier University Hospital, Montpellier, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceDepartment of Nephrology, Transplantation, Dialysis and Apheresis, Pellegrin Hospital, Bordeaux University Hospital, Bordeaux, FranceUMR CNRS 5164, ImmunoConcEpT, Bordeaux University, Bordeaux, FranceDepartment of Immunology, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, FranceDepartment of Immunology, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, FranceUMR CNRS 5164, ImmunoConcEpT, Bordeaux University, Bordeaux, FranceDepartment of Immunology and Immunogenetics, Pellegrin Hospital, Bordeaux University Hospital, Bordeaux, FranceSchool of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom0Department of Immunology, Hospital European Georges Pompidou, Paris, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceDepartment of Nephrology, Transplantation, Dialysis and Apheresis, Pellegrin Hospital, Bordeaux University Hospital, Bordeaux, FranceUMR CNRS 5164, ImmunoConcEpT, Bordeaux University, Bordeaux, FranceUniversity of Montpellier, Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, FranceINSERM U1183, Institute for Regenerative Medicine and Biotherapy, Saint-Eloi Hospital, Montpellier University Hospital, Montpellier, FranceC4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9—indicative of complement-mediated injury—is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25–73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9– ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients.https://www.frontiersin.org/article/10.3389/fimmu.2019.00235/fullantibody-mediated rejectionkidney transplantationcomplementC4dC5b9 |