Introduction: C4d (scare of C4 cleavage) deposition in peritubular capillaries (PTC), a marker of complement activation, is associated with antibody-mediated rejection (AMR) in kidney transplantation. However, its association with allograft survival is controversial. We hypothesized that the deposition of C5b-9 terminal complement complex is a severity marker in patients with C4d+ AMR.

Material and methods: We selected patients with an AMR diagnosis (according to Banff classification) in our center between January 2008 and December 2013. We excluded patients without available serum and/or biopsy. We performed C4d and C5b-9 staining by immunohistochemistry using monoclonal antibodies directed against C4d and C9 neoepitope.

Results: 26 patients were included. The median duration of follow-up was 50.5 months (range, 30.25 to 68.25). 25 patients (96%) had C4d deposition in glomerular capillaries and 21 (81%) in PTC. None patient had positive C5b-9 in PTC and 7 (27%) had C5b-9 deposition in glomerular capillaries (C5b-9g). Among them, 4 (15%) had global C5b-9g (>50% of the capillary loops of at least 1 glomerulus). All patients with C5b-9g had C4d deposition in glomerular and PTC. Death-censored graft survival was significantly lower in patients with global C5b-9g (median survival, 17 months versus 44 months; p= 0.01; figure 1). When adjusted by recipient characteristics, donor characteristics and immunosuppressive regimen, global C5b-9g remained an independent risk factor for death-censored graft loss (hazard ratio, 5.12; 95% confidence interval, 1.07 to 24.40; p= 0.04).Figure 1. Death-censored graft survival according to global C5b-9 deposition in glomerular capillaries (C5b-9g). AMR, antibody-mediated rejection.

Conclusion: Massive C5b-9 deposition – indicative of complement activation until the terminal pathway – in glomerular capillaries of patients with C4d+ AMR is associated with poor kidney allograft survival. Whether those patients should benefit of anti-C5 therapy should be assessed.

CITATION INFORMATION: Goutaudier V, Perrochia H, Marron-Wojewodzki M, Garo F, René C, Pirot N, Mourad G, Le Quintrec M. C5b-9 Deposition in Glomerular Capillaries Is Responsible for Poor Allograft Survival in Antibody-Mediated Rejection. Am J Transplant. 2017;17 (suppl 3).

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