Defining the phenotype of antibody-mediated rejection in kidney transplantation: Advances in diagnosis of antibody injury.

The diagnostic criteria for antibody-mediated rejection (ABMR) are constantly evolving in light of the evidence. Inclusion of C4d-negative ABMR has been one of the major advances in the Banff Classification in recent years. Currently Banff 2015 classification requires evidence of donor specific antibodies (DSA), interaction between DSA and the endothelium, and acute tissue injury (in the form of microvasculature injury (MVI); acute thrombotic microangiopathy; or acute tubular injury in the absence of other apparent cause). In this article we review not only the ABMR phenotypes acknowledged in the most recent Banff classification, but also the phenotypes related to novel pathogenic antibodies (non-HLA DSA, antibody isoforms and subclasses, complement-binding functionality) and molecular diagnostic tools (gene transcripts, metabolites, small proteins, cytokines, and donor-derived cell-free DNA). These novel tools are also being considered for the prognosis and monitoring of treatment response. We propose that improved classification of ABMR based on underlying pathogenic mechanisms and outcomes will be an important step in identifying patient-centered therapies to extend graft survival.