Beyond C4d: the ultrastructural appearances of endothelium in ABO-incompatible renal allografts

C4d is a marker of antibody-mediated rejection (ABMR). However, in ABO blood group incompatible (iABO) kidney transplants, the finding of positive C4d does not correlate with impaired graft function or histologic findings of antibody-mediated rejection by light microscopy. Brocker et al. looked further into ultrastructural findings of iABO grafts vs. ABO blood group compatible (cABO) grafts with positive C4d  vs. cABO grafts with negative C4d and no histologic findings of ABMR. iABO grafts had positive C4d in at least one of the biopsies. The authors did not find difference of ultrastructural findings between iABO and cABO group with negative C4d, in contrast to cABO with positive C4d in which more severe ultrastructural changes were seen and correlated with poor graft function/outcome. Accommodation was discussed as the reason for no deterioration of structure and function of iABO grafts with positive C4d.

C4d revisited

C4d is a byproduct of complement activation in classic and lectin pathway. It is non-functional but served as a robust evidence of antibody-mediated injury. It has been used as a tissue marker for antibody-mediated rejection (AMR) in kidney transplants for more than a decade. Its use has been extended to other transplant organs including heart, lung and pancreas though the liver grafts do not benefit from C4d yet.