TY - JOUR
T1 - Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival
AU - Wisse, Bram W.
AU - Kamburova, Elena G.
AU - Joosten, Irma
AU - Allebes, Wil A.
AU - van der Meer, Arnold
AU - Hilbrands, Luuk B.
AU - Baas, Marije C.
AU - Spierings, Eric
AU - Hack, Cornelis E.
AU - van Reekum, Franka E.
AU - van Zuilen, Arjan D.
AU - Verhaar, Marianne C.
AU - Bots, Michiel L.
AU - Drop, Adriaan C. A. D.
AU - Plaisier, Loes
AU - Seelen, Marc A. J.
AU - Sanders, Jan Stephan
AU - Hepkema, Bouke G.
AU - Lambeck, Annechien J. A.
AU - Bungener, Laura B.
AU - Roozendaal, Caroline
AU - Tilanus, Marcel G. J.
AU - Voorter, Christina E.
AU - Wieten, Lotte
AU - van Duijnhoven, Elly M.
AU - Gelens, Marielle A. C. J.
AU - Christiaans, Maarten H. L.
AU - van Ittersum, Frans J.
AU - Nurmohamed, Shaikh A.
AU - Lardy, Neubury M.
AU - Swelsen, Wendy
AU - van der Pant, Karlijn A. M. I.
AU - van der Weerd, Neelke C.
AU - ten Berge, Ineke J. M.
AU - Bemelman, Frederike J.
AU - Hoitsma, Andries J.
AU - van der Boog, Paul J. M.
AU - de Fijter, Johan W.
AU - Betjes, Michiel G. H.
AU - Heidt, Sebastiaan
AU - Roelen, Dave L.
AU - Claas, Frans H.
AU - Otten, Henny G.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - HLA
KW - ANTIBODIES
KW - STRENGTH
U2 - 10.1097/TP.0000000000002357
DO - 10.1097/TP.0000000000002357
M3 - Article
C2 - 30106794
SN - 0041-1337
VL - 103
SP - 789
EP - 797
JO - Transplantation
JF - Transplantation
IS - 4
ER -