Complement activation in antibody-mediated renal allograft rejection

J.J. Karijosemito, R.G.M. Lammerts, M.A.J. Seelen, M.R. Daha, A. Diepstra, J. van den Born, S.P. Berger, On behalf of COMBAT Consortium

Thursday 15 march 2018

15:15 - 15:20h at Willem Burger Foyer

Categories: Basic, Session (poster)

Parallel session: Poster session 4: Basic/translational research

Introduction

Antibody-mediated rejection (AMR) is an important barrier to improve long-term outcome in kidney transplantation. Diagnosis of AMR is based on detection of donor-specific antibodies (DSA’s) in the circulation, deposition of complement component C4d in peritubular capillaries and microvascular endothelial damage. Because of the involvement of the complement system, its components could be reliable biomarkers for the diagnosis of AMR. Therefore, the aim of this study was to find systemic evidence of complement system activation and urinary complement excretion in renal transplant recipients diagnosed with AMR.

Methods

For this study, 14 patients with AMR and 81 patients without AMR in an indication renal transplant biopsy were included. Plasma levels of complement component C3 were determined using radial-immunodiffusion assay (RID) and properdin, C3d and terminal component C5b-9 using enzyme-linked-immunosorbent assay (ELISA). Urinary excretion of properdin and C5b-9 was examined using ELISA.

Results

Plasma C3 was significantly lower (p<0.001) and plasma C3d was significantly higher (p=0.04) in AMR patients compared to non-AMR patients. C3d/C3 ratio was significantly higher in AMR compared to non-AMR (p=0.01). No differences were found for plasma properdin (p=0.14) and C5b-9 levels (p=0.13) between both groups. After correcting for 24h urinary creatinine excretion, urinary excretion of properdin (p=0.22) and C5b-9 (p=0.12) was similar between AMR and non-AMR patients.

Conclusion

Complement activation in AMR appears to be detectable in blood at the level of C3 and, surprisingly, without altered terminal complement activation. Assessment of C3 consumption may be advantageous in the diagnosis and follow up of AMR.