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.
N1 - Funding Information:
16Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. This study was supported by research funding from the Dutch Kidney Foundation Project code CP12.23 Risk Assessment of Kidney Graft Failure by HLA Antibody Profiling. The authors declare no conflicts of interest. B.W., E.K., A.D., L.P., and H.O. participated in research design. B.W., E.K., I.J., W.A., L.H., Av.Z., M.V., M.L.B., B.H., A.L., L.B., C.R., C.V., It.B., A.H., S.H., D.R., F.C., and H.O. participated in writing of the article. B.W., E.K., A.D., and L.P.
Publisher Copyright:
Copyright © 2018 The Author(s).
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 -