Pre-formed donor specific antibodies > 3000 MFI managed at the time of transplantation predicts early antibody-mediated rejection after heart transplantation in a large cohort of patients

Background The presence of untreated pre-formed donor specific anti-HLA antibodies (DSA) increases the risk of early antibody-mediated rejections (AMR) after heart transplantation (HTx) but no robust data concerning the Mean Fluorescence Intensity (MFI, a semi-quantitative evaluation of the amount of DSA) threshold is available. Purpose To analyse risk factors for early AMR after HTx and determine a threshold value of MFI in a large cohort of patients transplanted with pre-formed DSA managed with plasmapheresis and immunoglobulines at the time of transplantation. Methods We performed a retrospective single-center observational study. We included all consecutive patients with (1) a first non-combined HTx between 2009 and 2015, (2) pre-formed DSA > 1000 MFI (on historical or day 0 sera). The primary-endpoint was biopsy-proven AMR (pAMR1 to 3 according to ISHLT guidelines) at 1 year post-transplant (death-censored). Results A total of 194 patients met the inclusion criteria, including 181 patients with at least 1 endomyocardial biopsy (EMB) during follow-up. Thirty-seven patients were diagnosed with at least 1 episode of biopsy-proven AMR at 1 year. MFI of immunodominant pre-formed DSA was the only independent risk factor for biopsy-proven AMR (HR = 1.08 for 500-increment, 95% CI = 1.03–1.12). Optimal cut-off value of MFI of immunodominant DSA determined through ROC-curve analysis was 2913 (sensitivity = 0.46; specificity = 0.81 for biopsy proven AMR, AUC = 0.72, Fig. 1 ). Conclusion In a large cohort of patients transplanted with pre-formed DSA managed at the time of transplantation, MFI of immunodominant DSA was the only risk factor for early AMR. Optimal threshold to predict AMR was about 3000.