Deciphering antibody-mediated rejection: new insights into mechanisms and treatment

To outline recent studies describing the mechanisms of antibody-mediated rejection (AMR) and new clinical protocols aimed at prevention and/or treatment of this difficult clinical entity.

The natural history of acute AMR after positive cross-match kidney transplantation involves an acute rise in donor-specific alloantibody (DSA) in the first few weeks after transplantation. Whereas the exact cellular mechanisms responsible for AMR are not known, it seems likely that both pre-existing plasma cells and the conversion of memory B cells to new plasma cells play a role in the increased DSA production. One recent study suggested that combination therapy with plasmapheresis, high-dose IVIG and rituximab was more effective treatment for AMR than high-dose intravenous immunoglobulin (IVIG) alone, but the role of anti-CD20 antibody is still unclear. Two new promising approaches to AMR focus on depletion of plasma cells with the proteasome inhibitor, bortezomib, and the inhibition of terminal complement activation with a humanized, anti-C5 antibody, eculizumab.

The pathogenesis of AMR in several different clinical settings is becoming clearer and more effective treatments are being developed. Whether the prevention or successful treatment of AMR will decrease the prevalence of chronic injury and improved long-term graft survival will require longer-term studies.