Diagnosis of antibody-mediated rejection in cardiac transplantation: a call for standardization

Currently clinical antibody-mediated rejection (AMR) requires demonstration of histopathologic changes, presence of donor-specific allo-antibodies and allograft dysfunction to establish the diagnosis. Pathology practice patterns in the immunopathologic evaluation and interpretation of cardiac transplant biopsies vary. Specific recommendations for post-transplant allo-antibody monitoring are lacking. Recently, the occurrence of surveillance biopsies being positive for immunopathologic markers of AMR without concomitant graft dysfunction is increasingly recognized. This review focuses on issues of standardization in the diagnosis of AMR and the need for updated criteria.

Concomitant use of C4d and C3d proved to be strongly predictive of the presence of circulating allo-antibodies and allograft dysfunction in heart transplant recipients. Asymptomatic patients with histopathologic evidence of AMR in their biopsies appear to have increased risk for cardiac allograft vasculopathy and cardiovascular mortality. The role of nonhuman leukocyte antigen antibodies in AMR has not been adequately addressed.

A consensus on the frequency of AMR screening, antibody panels, interpretation and reporting of stains will enhance standardization of the diagnosis of AMR. Further studies are needed to define asymptomatic or subclinical AMR and to determine the long-term outcome of pathologic evidence of complement activation without allograft dysfunction.