Early screening for antibody-mediated rejection in heart transplant recipients.

Kfoury AG, Hammond ME, Snow GL, Stehlik J, Reid BB, Long JW, Gilbert EM, Bader FM, Bull DA, Renlund DG. Early screening for antibody-mediated rejection in heart transplant recipients. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2007 Dec 1; 26(12):1264-9.

Related HSR&D Project(s)

• RRP 07-276 – Advanced Heart Failure Outreach

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Abstract:

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 ( > or = 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 > or = 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.