Toward a sensible single antigen bead cut-off based on kidney graft survival

BACKGROUND: There is no consensus in the literature on the interpretation of single antigen bead (SAB) positive for a specific HLA antibody. METHODS: To inform the debate, we studied the relationship between various SAB positivity algorithms and the impact of resulting donor-specific HLA antibody (DSA) positivity on long-term kidney graft survival in 3237 deceased-donor transplants. RESULTS: First, we showed that the interassay variability can be greatly reduced when working with signal-to-background ratios instead of absolute MFIs. Next, we determined pretransplant DSA using various MFI cut-offs, signal-to-background ratios (STBR) and combinations thereof. The impact of the various cut-offs was studied by comparing the graft survival between the DSA-positive and DSA-negative groups. We did not observe a strong impact of various cut-off levels on 10-year graft survival. A stronger relationship between the cut-off level and 1-year graft survival for DSA-positive transplants was found when using STBR, most pronounced for the bead of the same HLA-locus with lowest MFI taken as background. CONCLUSIONS: With respect to pretransplant risk stratification, we propose a SBTR-6 (using the bead of the same HLA-locus with lowest MFI as background) cut-off of 15 combined with an MFI cut-off of 500, resulting in 8% and 21% lower 1- and 10-years graft survival, respectively, for 8% DSA positive transplants