Donor-specific HLA alloantibodies: long-term impact on cardiac allograft vasculopathy and mortality after heart transplant.

OBJECTIVES: The clinical significance of anti-HLA-alloantibodies remains controversial. Recent studies have linked development of donor-specific HLA-antibodies to chronic allograft rejection and graft loss after heart, kidney, and lung transplants. We investigated the clinical impact of donor-specific humoral alloreactivity during the follow-up of heart transplant recipients. PATIENTS AND METHODS: The sera of 213 heart transplant recipients were screened by enzyme-linked immunosorbent assay for HLA-antibody production. The antigen specificity of the detected HLA class I and class II antibodies was identified using a Luminex assay. Outcome variables were survival, cardiac allograft vasculopathy, and cellular rejection. RESULTS: The cumulative incidence of alloantibody formation was 23/213 patients (10.8%). The majority of detected alloantibodies were donor-specific for HLA class II. Mean follow-up at antibody measurements was 7 -/+ 4.9 years. Freedom from vasculopathy at 5 and 10 years was 77.9% and 26% in donor-specific HLA-antibody-positive patients compared with 84.6% and 65.2% in antibody-negative controls (P = .025). Freedom from treated, biopsy-proven rejection was 44.4% for donor-specific HLA-antibody-positive patients compared with 70.2% in the controls (P = .06). Multivariate analyses identified donor-specific HLA antibody positivity as an independent risk factor for vasculopathy. CONCLUSIONS: Our results demonstrate a strong correlation between the development of donor-specific HLA antibodies and adverse outcomes after heart transplant. Detection of donor-specific HLA antibodies might identify high-risk patients and offer an opportunity for early clinical intervention and modification of immunosuppression.