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Autoantibodies in Kidney Diseases

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00235

C5b9 deposition in glomerular capillaries is associated with poor allograft survival in antibody-mediated rejection of kidney allograft

 Valentin Goutaudier1,  Hélène Perrochia1, Simon Mucha2, Marie Bonnet1, Sylvie Delmas1, Florian Garo1, Valérie Garrigue1, Sébastien Lepreux2,  Vincent Pernin1, Jean-Emmanuel Serre1, Ilan Szwarc1,  Pierre Merville2, Annie Ramounau-Pigot1, Céline René1, Jonathan Visentin2,  Bryan P. Morgan3,  VERONIQUE FREMEAUX-BACCHI4, Georges Mourad1,  Lionel Couzi2 and Moglie Le Quintrec1*
  • 1Centre Hospitalier Universitaire de Montpellier, France
  • 2Centre Hospitalier Universitaire (CHU) de Bordeaux, France
  • 3Cardiff University, United Kingdom
  • 4Hôpital Européen Georges-Pompidou (HEGP), France

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 versus 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.

Keywords: Antibody-mediated Rejection, Kidney Transplantation, complement, C4d complement deposition, c5b9

Received: 16 Nov 2018; Accepted: 28 Jan 2019.

Edited by:

Bradley P. Dixon, Children's Hospital Colorado, United States

Reviewed by:

Bassam G. Abu Jawdeh, University of Cincinnati, United States
Gaurav Gupta, Virginia Commonwealth University, United States  

Copyright: © 2019 Goutaudier, Perrochia, Mucha, Bonnet, Delmas, Garo, Garrigue, Lepreux, Pernin, Serre, Szwarc, Merville, Ramounau-Pigot, René, Visentin, Morgan, FREMEAUX-BACCHI, Mourad, Couzi and Le Quintrec. 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.

* Correspondence: Prof. Moglie Le Quintrec, Centre Hospitalier Universitaire de Montpellier, Montpellier, France,