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; Marielle 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

doi:10.1097/TP.0000000000002357

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, Marielle 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

23 Citations (Web of Science)

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 language	English
Pages (from-to)	789-797
Number of pages	9
Journal	Transplantation
Volume	103
Issue number	4
DOIs	https://doi.org/10.1097/TP.0000000000002357
Publication status	Published - Apr 2019

Keywords

HLA
ANTIBODIES
STRENGTH

Access to Document

10.1097/TP.0000000000002357

Cite this

Wisse, B. W., Kamburova, E. G., Joosten, I., Allebes, W. A., van der Meer, A., Hilbrands, L. B., Baas, M. C., Spierings, E., Hack, C. E., van Reekum, F. E., van Zuilen, A. D., Verhaar, M. C., Bots, M. L., Drop, A. C. A. D., Plaisier, L., Seelen, M. A. J., Sanders, J. S., Hepkema, B. G., Lambeck, A. J. A., ... 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

@article{e16d8b5066374c3d944aa1bcbb23e2b2,

title = "Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival",

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.",

keywords = "HLA, ANTIBODIES, STRENGTH",

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

year = "2019",

month = apr,

doi = "10.1097/TP.0000000000002357",

language = "English",

volume = "103",

pages = "789--797",

journal = "Transplantation",

issn = "0041-1337",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "4",

}

Wisse, BW, Kamburova, EG, Joosten, I, Allebes, WA, van der Meer, A, Hilbrands, LB, Baas, MC, Spierings, E, Hack, CE, van Reekum, FE, van Zuilen, AD, Verhaar, MC, Bots, ML, Drop, ACAD, Plaisier, L, Seelen, MAJ, Sanders, JS, Hepkema, BG, Lambeck, AJA, Bungener, LB, Roozendaal, C, Tilanus, MGJ, Voorter, CE , Wieten, L , van Duijnhoven, EM , Gelens, MACJ, Christiaans, MHL, van Ittersum, FJ, Nurmohamed, SA, Lardy, NM, Swelsen, W, van der Pant, KAMI, van der Weerd, NC, ten Berge, IJM, Bemelman, FJ, Hoitsma, AJ, van der Boog, PJM, de Fijter, JW, Betjes, MGH, Heidt, S, Roelen, DL, Claas, FH & Otten, HG 2019, 'Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival', Transplantation, vol. 103, no. 4, pp. 789-797. https://doi.org/10.1097/TP.0000000000002357

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 -