C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection

• Main Authors: Valentin Goutaudier, Hélène Perrochia, Simon Mucha, Marie Bonnet, Sylvie Delmas, Florian Garo, Valérie Garrigue, Sébastien Lepreux, Vincent Pernin, Jean-Emmanuel Serre, Ilan Szwarc, Pierre Merville, Annie Ramounau-Pigot, Céline René, Jonathan Visentin, Bryan Paul Morgan, Véronique Frémeaux-Bacchi, Georges Mourad, Lionel Couzi, Moglie Le Quintrec
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-03-01
• Series: Frontiers in Immunology
• Subjects: antibody-mediated rejection; kidney transplantation; complement; C4d; C5b9
• Online Access: https://www.frontiersin.org/article/10.3389/fimmu.2019.00235/full

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.