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. BungenerCaroline 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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)789-797
JournalTransplantation
Volume103
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019

Cite this

Wisse, B. W., Kamburova, E. G., Joosten, I., Allebes, W. A., van der Meer, A., Hilbrands, L. B., ... Otten, H. G. (2019). Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival. Transplantation, 103(4), 789-797. https://doi.org/10.1097/TP.0000000000002357