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Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival

Bram W Wisse, Elena G Kamburova, Irma Joosten, Wil A Allebes, Arnold van der Meer, Luuk B Hilbrands, Marije C Baas, Eric Spierings, Cornelis E Hack, Franka E van Reekum, Arjan D van Zuilen, Marianne C Verhaar, Michiel L Bots, Adriaan C A D Drop, Loes Plaisier, Marc A J Seelen, Jan Stephan Sanders, Bouke G Hepkema, Annechien J A Lambeck, Laura B Bungener, Caroline Roozendaal, Marcel G J Tilanus, Christina E Voorter, Lotte Wieten, Elly M van Duijnhoven, Mariëlle A C J Gelens, Maarten H L Christiaans, Frans J van Ittersum, Shaikh A Nurmohamed, Neubury M Lardy, Wendy Swelsen, Karlijn A M I van der Pant, Neelke C van der Weerd, Ineke J M Ten Berge, Frederike J Bemelman, Andries J Hoitsma, Paul J M van der Boog, Johan W de Fijter, Michiel G H Betjes, Sebastiaan Heidt, Dave L Roelen, Frans H Claas, Henny G Otten

Published: 01/04/2019

bstract

Background: There is no consensus in the literature on the interpretation of single-antigen bead positive for a specific HLA antibody.

Methods: To inform the debate, we studied the relationship between various single-antigen bead 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 median fluorescence intensities (MFIs). Next, we determined pretransplant DSA using various MFI cutoffs, signal-to-background ratios, and combinations thereof. The impact of the various cutoffs was studied by comparing the graft survival between the DSA-positive and DSA-negative groups. We did not observe a strong impact of various cutoff levels on 10-year graft survival. A stronger relationship between the cutoff level and 1-year graft survival for DSA-positive transplants was found when using signal-to-background ratios, 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 signal-to-background ratio-6 (using the bead of the same HLA-locus with lowest MFI as background) cutoff of 15 combined with an MFI cutoff of 500, resulting in 8% and 21% lower 1- and 10-year graft survivals, respectively, for 8% DSA-positive transplants.

Full Access Link: Transplantation