Antibody-mediated injury in the renal allograft

Antibody-mediated renal allograft injury can give rise to a range of histological and ultrastructural changes, with or without C4d deposition. The changes associated with alloantibody can be seen on surveillance biopsies in patients with normal graft function or on clinically indicated biopsies. In this case report, we review a series of biopsies at different time points, from 1 month to 2 years after transplantation, from a single kidney allograft in a patient who had donor-specific alloantibody (DSA) before transplantation. In the early posttransplant period, the patient was at risk for acute humoral rejection, with high serum DSA levels and C4d deposition in the graft, but acute humoral rejection was averted by early use of a C5 inhibitor drug. Later, while maintaining stable graft function, the patient developed the following biopsy features of chronic antibody-mediated injury: peritubular capillaritis, peritubular capillaropathy (peritubular capillary basement membrane multilamination) seen by electron microscopy, and early transplant glomerulopathy, along with activated endothelial cells detected by electron microscopy. Late biopsies did not show C4d deposition, and the patient had low serum DSA levels, raising the possibility that noncomplement-mediated pathways may be involved in late antibody-mediated allograft injury. The pathologist can recognize changes attributable to alloantibody and distinguish these features from T-cell-mediated rejection, which will allow for appropriate treatment of these patients.