Early Screening for Antibody-mediated Rejection in Heart Transplant Recipients

Background: The International Society for Heart and Lung Transplantation (ISHLT) recently established a diagnostic scheme for antibody-mediated rejection (AMR). Currently, however, confirmatory immunohistochemistry studies are recommended only if AMR is clinically or histologically suspected. In this study, we examine whether a pattern of repetitive AMR occurred early enough after transplantation to warrant prospective immunohistochemistry screening in all recently transplanted recipients. Methods: We queried our pathology database of adult and pediatric endomyocardial biopsies (EMBs) from 1985 to 2005. All EMB specimens were prospectively studied by immunofluorescence in the early post-operative period. AMR was defined as the presence of complement and immunoglobulin deposits on frozen section. Only patients classified as antibody-mediated rejectors (≥3 episodes of AMR) were included. Cumulative incidence and time from transplant to first and third AMR episodes were obtained. Results: Three hundred seventy-five of 870 heart transplant recipients had ≥3 episodes of AMR. Mean age of recipients was 45.6 years and 78% were male. A total of 19,569 EMBs comprised the study data. By 100 days post-transplant, 85% of patients had their first and 54% their third AMR. In addition, patients showed a clear trend of early clustering of AMR-positive biopsies. Results were similar regardless of whether or not muromonab-CD3 (Orthoclone OKT3) induction was used. Conclusions: We advocate early immunohistochemical surveillance testing for AMR to supplement the diagnostic algorithm established by the ISHLT, because a pattern of AMR becomes manifest soon after transplantation. This change will allow earlier detection of asymptomatic AMR and may prompt changes in immunosuppression strategies to avoid adverse outcomes.